Gibberellins in Penicillium strains: Challenges for endophyte-plant host interactions under salinity stress

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ContentslistsavailableatScienceDirect

Microbiological

Research

jo u r n al ho m e p ag e :w w w . e l s e v i e r . c o m / l o c a t e / m i c r e s

Gibberellins

in

Penicillium

strains:

Challenges

for

endophyte-plant

host

interactions

under

salinity

stress

Ana

Lúcia

Leitão

a,∗

_,

_Francisco

_J.

_Enguita

b

a_MEtRICs,_Departamento_de_Ciências_e_Tecnologia_da_Biomassa,_Faculdade_de_Ciências_e_Tecnologia,_Universidade_NOVA_de_Lisboa,_Campus_de_Caparica, 2829-516Caparica,Portugal

b_Faculdade_de_Medicina,_Universidade_de_Lisboa,_Av._Prof._Egas_Moniz,_Lisboa_1649-028,_Portugal

a

r

t

i

c

l

e

i

n

f

o

Articlehistory:

Received9November2015 Accepted14November2015 Availableonline1December2015 Keywords: Penicillium Plants Salinity Gibberellins Symbioticinteractions

a

b

s

t

r

a

c

t

ThegenusPenicilliumisoneofthemostversatile“mycofactories”,comprisingsomespeciesableto pro-ducegibberellins,bioactivecompoundsthatcanmodulateplantgrowthanddevelopment.Although plantshavetheabilitytosynthesizegibberellins,theirlevelsarelowerwhenplantsareundersalinity stress.Ithasbeenrecognizedthatdetrimentalabioticconditions,suchassalinestress,havenegative effectsonplants,beingtheavailabilityofbioactivegibberellinsacriticalfactorfortheirgrowthunder thisconditions.ThisreviewsummarizestheinterplayexistingbetweenendophyticPenicilliumstrains andplanthostinteractions,withfocusonbioactivegibberellinsproductionasafungalresponsethat allowsplantstoovercomesalinitystress.

Contents

1. Introduction...8

2. Gibberellinsasmodulatorsofplant-endophyteinteractions...9

2.1. Fungalendophytes ... 9

2.2. Gibberellinsasphytohormones...9

2.3. Moleculardetailsofgibberellinaction...9

3. Fungiasgibberellinproducers:biosyntheticgeneclusters...10

4. GenusPenicillium...11

5. Salinestress,gibberellinsandPenicillium...13

5.1. Salinity ... 13

5.2. InteractionsbetweenPenicilliumandplantsthroughgibberellins...14

5.3. PutativegibberellinbiosyntheticgenesinPenicillium...15

6. Conclusionsandfutureperspectives...16

References...16

1. Introduction

Fungiareimportantmicrobialfactoriesofbioactive

extracel-lularmetabolitesor “extrolites”,namelysecondarymetabolites.

Enzymes, immunosuppressive agents, antitumor agents,

antibi-otics,vitamins,andpigments,areexamplesoftherepresentative

panoplyofproductswithincreasinginteresteitherforscientiﬁc

∗ Correspondingauthor.Fax:+351212948543. E-mailaddress:aldl@fct.unl.pt(A.L.Leitão).

communityorindustrialsector(Brakhage,2013;Correaetal.,2014;

Kimetal.,2014;LeitãoandEnguita,2014;Quangetal.,2014).

Thegibberellins,hormonessynthesizedbyplants,are

interest-ingextrolitesalsoproducedbysomestrainsoffungilikeFusarium

sacchari,Fusariumkonzum,Fusariumsubglutinans,Aspergillus

fumi-gatus,PenicilliumjanthinellumandPenicilliumresedanum,among

others(Troncosoetal.,2010;Khanetal.,2011b,2015a,b).The

gib-berellinsarerelatedbytheirchemicalstructure (resultingfrom

isoprenepolymerization)andtheirbiosynthesispathway(origin

inhydroxymethyl-glutarylcoenzymeA),butonlyfewofthemare

bioactive.Oneofthesebioactivegibberellinsisthegibberellicacid,

oftencalledGA3;curiouslysomefungalstrainsareabletoproduce

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higherquantitiesofGA3whencomparedtoplants(Heddenetal., 2001).

Theuseof fungalendophytesand theirextrolites canbean

excellentopportunitytominimizethenegativeeffectofabiotic

factors,suchassalinity,oncropyield.Theterm

“plant-growth-promoting-fungi”wasestablishedtodesignatesomerhizosphere

fungiabletopromoteadirecteffectonplantgrowthuponroot

col-onizationorbythetreatmentwiththeirmetabolites(Hossainetal.,

2014).Recentstudies have revealedthat Penicillium endophyte

couldsupplygibberellinstoplanthost,whichisparticularly

impor-tantwhenplantisunderbioticorabioticstress.Inthisreview,we

summarizerecentdiscoveriesontheendophyticPenicilliumstrains

andplanthostinteractions,withemphasisonbioactivegibberellins

asresponsetosaltstress.

2. Gibberellinsasmodulatorsofplant-endophyte interactions

2.1. Fungalendophytes

Fungalendophytesrefertothefungiwhichinvadeorliveinside

the tissues of plants without causing apparent harm to them

(Chandra,2012).Theyweredescribedbytheﬁrsttimein1904in

thedarnel,Loliumtemulentum(Freeman,1904),buttheydidnot

receivemuchattentionuntiltherecentdevelopmentofscreening

technologiesthatrevealedtheirgreatpotentialasamainsourceof

extroliteswithpromisingagriculturalandpharmaceutical

appli-cations(Tanand Zou, 2001; Kusari etal., 2012).Therefore,the

relationshipbetweentheendophyteandtheplantisgenerally

con-sideredmutualisticbecausetheendophytesigniﬁcantlyimproves

hostplanttolerancetoabioticstressessuchasdroughtand

water-deﬁcitorbioticfactorssuchasinsects,vertebrateherbivoresand

nematodes,alongwithincreasedresistanceandpromotingplant

growth,nutrientsuptake,andwaterresourceuse;andinturnthe

plantprovidesthemicroorganismwithnutrients,protection,and

efﬁcientdissemination(Schardlet al.,2004).However,theidea

thattherearenoneutralinteractionsbutratherthat

endophyte-hostrelationshipisabalancedsymbioticcontinuumrangingfrom

mutualismthroughcommensalismtoparasitism,isgaining

follow-ers(Alyetal.,2011).Infact,wheninsidetheplant,fungiassume

aquiescentstateuntilenvironmentalconditionsarefavorablefor

theirgrowth.Thefungihavetheabilitytocolonizetheplantmostly

byassociationwithbut insomecasescan liveinsidetheplant

eitherpenetratinginsidetherootcortexorintheaerialpartsof

theplant,duetotheirextracellularenzymaticsystem(Waqasetal.,

2012;Khanetal.,2013a).Aftercolonizationfungigrowwellinthe

apoplasticwashingﬂuidofthehost(Chandra,2012).

The fungal endophyte-plant host relationship seems to be

tightly dependent ongenetic, physiological and environmental

control(Kogeletal.,2006).Despiteofthat,thereisnodoubtthat

inthecaseof mutualisticinteractionthepresence ofthe

endo-phytehelpstomitigatetheeffectsofplantstresses,whichrequires

acontinualmetabolicinteractionbetweenfungusandplanthost.

Endophyticfungihaveastrongtolerancetowardsplant´ıs

metabo-litesduetotheirabilitytotransformanddetoxifythemwiththe

concomitant production ofextrolites, some of themwith great

pharmaceuticalpotentialas bioactivecompounds(Kusari etal.,

2012;Khanetal.,2015b).

In some cases from endophyte-host relationship results

metabolitesthatareproducedsimultaneouslybytheplantandthe

fungus,likethephytohormonesgibberellins(Takedaetal.,2015).

Twooppositetheoriestriedtoexplainthiscuriousphenomenon.

Onesupportstheideathatendophyteevolvedgibberellins

biosyn-thetic pathwaysindependently fromplants, based on the high

conservationofgibberellinsclusterorganizationinPhaeosphaeria

spp. and Sphaceloma manihoticola, two distantly related fungal

species. Thedifferences betweenplants andfungi at

biochemi-cal and geneticlevels strengthensthat higher plants and fungi

haveevolvedtheirbiosyntheticpathwaystogibberellins

indepen-dently(MacMillan,1997;Heddenetal.,2001;Yamaguchi,2008;

BomkeandTudzynski,2009).Theotheronepointoutthatduring

theco-evolutionofmicroorganismsandtheirhostplants,

endo-phytesundergogeneticmodiﬁcation,for instanceby hostgene

transfer,thatallowthemtoadaptsuccessfullytotheplant

microen-vironments,whichcouldbealsocorroboratedbythelackofplant

responseagainstthepresenceofendophytes(ChapmanandRagan,

1980;Germaineetal.,2004).

2.2. Gibberellinsasphytohormones

Gibberellinswereﬁrstidentiﬁedasphytohormonesinthe1930s

basedonanover-growthriceseedlingduetoinfectionsbyFusarium

fujikuroi(teleomorphGibberellafujikuroi)a pathogenicrice

fun-gus(Ogas,2000).Thesefungalsecondarymetaboliteshavebeen

reportedtoplayapivotalroleinplantgrowthanddevelopment

processes,suchasregulationofgeneexpressioninthecereal,seed

germination,stemelongation,ﬂoweringandfruitdevelopment.In

thepresenceofgibberellins,plantsareabletoaltertheir

physiol-ogyandbiochemistryinrapidresponsetoenvironmentalchanges

(Olszewskiet al., 2002).Gibberellins were merely isolated and

identiﬁedasplanthormonefromextractsofhigherplantsinthe

mid-50sbyBritishscientists(Lang,1956;Radley,1956).The

knowl-edgeofgibberellicacid(GA3)structurefromG.fujikuroiopened

thewindowfornewstudiesthatculminatedwiththediscovery

thatgibberellinswerediterpenoidcompounds(Birchetal.,1958;

Crossetal.,1959).Furtherstudiesweredone,mostofthemwith

the mutant BI-41a (GA-deﬁcientmutant of G. fujikuroi blocked

atanearlystepofthepathway), andbringtolight the

biosyn-theticpathwayofgibberellicacidintheG.fujikuroi(Bearderetal.,

1974;Bearder,1983).During severalyears, gibberellinpathway

wasonlyreportedintheF.fujikuroi.Detailedcharacterizationat

chemical,biochemicaland geneticlevelsinF.fujikuroihasbeen

reported(Cerda-Olmedoetal.,1994;Tudzynski,2005;Bomkeand

Tudzynski,2009).TheGA3biosynthesis,forexample,involvetwo

early cyclizationreactions, from geranylgeranyl diphosphate to

ent-kaurene,followedbyseveraloxidativereactionscatalyzedby

cytochrome P450monooxygenases torender theﬁnal product,

19–10␥-lactone(Kellerand Hohn,1997;TudzynskiandHolter,

1998).

Thegibberellinsaresmallmoleculesofalargegroupof

tetra-cyclicditerpenoidcarboxylicacids,beingdeﬁnedbytheirchemical

structure based on the ent-gibberellane carbon skeleton and

assignedgibberellin“numbers”dependingonchronologicalorder

oftheiridentiﬁcation.Nowadays,thereare136knowngibberellins

producedbyfungi,plantsandevenbacteria.Nevertheless,onlya

smallnumberofthem,suchasGA1,GA3,GA4andGA7are

promi-nentbioactive(Davies,2004).

2.3. Moleculardetailsofgibberellinaction

Asphytohormones, gibberellins regulatecritical stepsin the

plantlife cycle. Theirphysiological action is mainlyexertedby

counteractingtheinhibitoryeffectofDELLAproteins,afamilyof

nuclearnegativeregulatorsthatrestrictplantgrowthprobablyby

transcriptionalreprogramming(Fig.1)(Sun,2011).DELLAproteins

areexpressedunderosmoticortemperaturestress,repressingthe

plantgrowth.ExposureofArabidopsisthalianatosaltstress

trig-gersareductioninbioactivegibberellins,promotesDELLA(groupof

transcriptionalregulators)accumulationandconsequently

DELLA-mediatedgrowthrestriction(Achardetal.,2006).Althoughitis

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Fig.1. Actionmechanismofgibberellins.Gibberellins(GA)actionisexertedbybindingtotheGID1nuclearreceptor,andsubsequentrecruitmentofDELLAproteins.The formationoftheternarycomplex,GA-GID1-DELLA,facilitatestheactionoftheubiquitintransferaseSCF,whichactsoverDELLAproteinsandinducestheirdegradationvia 26Sproteasome.Gibberellinscanbesynthesizeddirectlybyplantsorbyendophyticmicroorganisms,namelyfungi,counteractingtheinhibitoryeffectsofDELLAproteins overtheplantgrowingsignals.Underabioticstressconditions,severalgibberellin-inactivatingenzymesareproduced,suchasgibberellin-oxidases(GA2ox).

cascadeofinteractionsinvolvinggibberellinsandotherhormone

signalling pathways, the regulationof expressionor activity of

transcriptionsfactors involved in gibberellinmetabolism genes

couldrepresentonemechanismofstresstoleranceinplants.At

thesametime,theabioticformofstressisabletoinduceaseries

ofenzymeswhichareinvolvedintheinactivationofgibberellins,

namelygibberellin-oxidases(Rieuetal.,2008).Activeformsof

gib-berellins(namedGA1,GA3,GA4andGA7)actviaGID1proteins,a

familyofspeciﬁcnuclearreceptorsthatplayanimportantrolein

regulatingdifferentdevelopmentalprocessesinplants(

Ueguchi-Tanakaetal.,2007;Voegeleetal.,2011).Gibberellinbindingto

GID1receptorinducesaconformationalchangeintheproteinthat

makesitpronetointeractwiththeN-terminaldomainofDELLA

repressors.Gibberellinsoffungaloriginsharethesamefunctional

characteristicsoftheplantgibberellins,sincetheyareidenticalin

theirchemicalstructure(Khanetal.,2013b).Aftertheinteraction

withgibberellins,theGID1-DELLAcomplexissubsequently

ubiq-uitinatedbytheubiquitin-transferaseSCF,andthustargetedfor

proteindegradationmediatedbythe26Sproteasome.In

conse-quence,thegibberellinactionresultsinreducedlevelsoftheDELLA

repressorandastimulationofplantgrowth(Fig.1).

The detailed molecular mechanism of the

gibberellin-GID1-DELLAinteractionhasbeencharacterizedbyX-raycrystallography

studies(Fig.2)(Muraseetal.,2008;Shimadaetal.,2008).

Com-plexescontaininggibberellinsGA3andGA4,theGID1receptorand

theN-terminalDELLAdomainhavebeenresolvedathigh

resolu-tion,showinganintimateinteractionbetweenthereceptorand

thegibberellinmolecule,establishedinadeepproteinpocketand

basedmainlyonhydrophobicinteractions(Fig.2)(Muraseetal.,

2008).However,thelackofthestructuralinformationonthe

apo-receptorpreventedtounderstandthedynamicsofitsinteraction

withthegibberellinligandandthesubsequentbindingtothe

N-terminalDELLAdomain.

3. Fungiasgibberellinproducers:biosyntheticgene clusters

Several species of fungi belonging to the geni Fusarium,

Aspergillus and Penicilliumhave beencurrentlycharacterizedas

gibberellinproducers(Tudzynski,2005).Thecanonicalpathway

for gibberellinbiosynthesisin fungiwasoriginallydescribed in

F. fujikuroi and their molecular details and involved enzymes

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Fig.2. StructuraldeterminantsforthegibberellinactionasdeterminedbyX-raycrystallography.(A)ribbonrepresentationoftheGA3-GID1-DELLA(PDBcode:2ZSH), showingtheGID1structurewiththebindingpocketwheregibberellinGA3islocated,andalsotheN-terminaldomainofDELLA.Thegraphwaspreparedbyusingthe CCP4MGsoftware(McNicholasetal.,2011).(B)planardiagramofmolecularinteractions(Ligplotdiagram)occurringinthesubstratebindingpocketofGID1receptor involvedintherecognitionofgibberellinGA3.Atomsinvolvedinhydrogenbondsbetweenthereceptorandtheligandaredepictedforeachaminoacidandrepresentedby dottedlines.Hydrophobicinteractionsaredepictedonlybythenumberandtypeofresidueinvolved.ThepanelwasdesignedandeditedbytheLigplot+software(Laskowski andSwindells,2011).

2009). Gibberellins, like other diterpenoid compounds, are

synthesized starting from geranyldiphosphate (GDP), farnesyl

diphosphate(FDP)andgeranylgeranyldiphosphate(GGDP).This

lastcompound isaprecursor forgibberellinsandalsofor some

carotenoidsandubiquinones.Infungiandplants,GGDPiscyclized

to produce ent-kaurene, the ﬁrst gibberellin-speciﬁc precursor,

whichwillsuffersequentialoxidationstogenerateGA12-aldehyde

(Fig.2).Fungalgibberellinbiosyntheticpathwaywillconvert

GA12-aldehydeintoGA14-aldehydebyanoxidationreactioncatalyzed

bya cytochromeP450protein.Furtheroxidation and

desatura-tionreactionswillproducethegibberellinsGA1,GA3,GA4andGA7

(Tudzynski,2005;BomkeandTudzynski,2009).

Despitethebiochemicalcharacterizationofgibberellin

biosyn-theticpathwayinfungi,thegeneticbackgroundiscomparatively

lessknown.In F.fujikuroithegibberellinbiosyntheticclusteris

comprisedbysevenclusteredgenesencodingfourcytochrome

P-450oxidoreductases(P450-1, P450-2,P450-3and P450-4), two

GGDPsynthases(Ent-kaur-16-enesynthase,CPS/KS,and

geranyl-geranyldiphosphatesynthase,GGS2),andaGA4desaturase(DES).

BesidesspeciesbelongingtotheFusariumgenus,thereareonlytwo

documentedcasesofthegeneticcharacterizationofagibberellin

biosyntheticgeneclusterinSphaceloma(Bomkeetal.,2008)and

Phaeosphaeria(Kawaideetal.,1997,2000).Theevolutionary

mech-anismsbywhichthesefungiacquiredthegibberellinbiosynthetic

geneclustersarenotyetclear.Anincreasingnumberofevidences

pointedoutthat thepresenceofhomologousbiosyntheticgene

clustersindistantlyrelatedfungicanprobablyresultfrom

horizon-talgenetransfer(SlotandRokas,2011).Interestingly,recentdata

alsoindicated thepresenceofdefectiveortruncatedgibberellin

biosyntheticclustersinsomeFusariumspecies(Wiemannetal.,

2013).Theseincompleteclustersareprobablyrelatedwith

adap-tivephenomenainthesefungalspecies,whichexertedselection

pressureforspeciﬁcgenedeletion(Maloneketal.,2005).In

Fusar-iummangiferae,FusariumcircinatumandsomestrainsofFusarium

oxysporum,thegibberellingbiosyntheticclusterispresentbutits

expression prevented by a non-functional promoter (Wiemann

et al.,2013).Silentbiosynthetic clusterslikethose observed in

someFusariumspecies arevery commonamong fungi,andcan

opennewpossibilitiesofgeneticmanipulationfortheproductionof

secondarymetaboliteslikegibberellins(LeitãoandEnguita,2014).

4. GenusPenicillium

Penicillium belongs tothe phylum Ascomycota, however its

taxonomic characterization is still a matter of discussion and

the difﬁculties in identifying most Penicillium species requires

multidisciplinaryapproaches.Clariﬁcationofspeciesconceptsin

the genus Penicillium was supported mainly by morphological

characteristics.RaperandThom,forexample,basedPenicillium

tax-onomyclassiﬁcationonthecombination ofmacroscopical(such

as colony texture and color) with micromorphological features

(RaperandThom,1949).InRaperandThomclassiﬁcation,Penicillia

thatproducemonoverticillateconidiophoreswereincludedinthe

Monoverticillatagroupandthisgroupwasdividedintonineseries

(genussubdivision).LaterinPitt’sclassiﬁcationmodiﬁcationson

serieswereperformedandsectionswereintroducedinsubgenus

basedonthepresenceofaswellingatthestipeapex(Pitt,1979).

Despite ofdirectidentiﬁcationof purePenicilliumspecies being

possiblebyimageanalysis(Dorgeetal.,2000);conidialcolor,

pro-ductionofascomataandascospores,shapeandornamentationof

conidiaandgrowthratesonsolidmediaremainrelevant

parame-tersforspeciesidentiﬁcation(Houbrakenetal.,2012).Houbraken

etal.(2011)basedonamultigeneapproachredeﬁnedthegenus

Penicilliumusing singlenamenomenclature and includingboth

asexualandsexualreproducingspecies.Theyproposedasectional

classiﬁcationandsubdividedPenicilliumintotwosubgeneraand25

sections(Houbrakenetal.,2011).

ThegenusPenicilliumhasreceivedmuchattentionduetohave

the bestknown producerof the antibioticpenicillin,P.

chryso-genum.Later,mycotoxinsbecamefocuseduponastheyappeared

intheprocessingorripeningofhumanfoods,beingamajorrisk

forhumanhealthduetotheircytotoxicity(KellerandHohn,1997).

However,Penicilliumspeciesarealsowellknownaspotentialtool

intheenvironmentﬁeld,sincetheyhavetheabilitytodegrade,or

toremoveawidevarietyofcompoundsandheavymetals(Leitão,

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bio-Fig.3.GibberellinbiosyntheticpathwayinFusariumfujikuroiandputativegibberellinbiosyntheticgenesinseveralPenicilliumspecies.A,gibberellinbiosyntheticpathway ascharacterizedinF.fujikuroiincludingtheinvolvedenzymes;GGDP,geraryl-geranyldiphosphate;EK,ent-kaneurin;EKA,ent-kaneuroicacid;GA14-ald,GA-14aldehyde. B,sequencealignmentofP450-1proteinfromF.fujikuroiwithitsputativeorthologsinseveralPenicilliumspecies.Conservedresiduesalongthesequencearedepictedinred boxes.(Forinterpretationofthereferencestocolorinthisﬁgurelegend,thereaderisreferredtothewebversionofthisarticle.)

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logicalactivityofPenicilliumstrainscanreducethegenotoxicity

inducedbyseveraltoxiccompounds(Pereiraetal.,2014;

Romero-Aguilaretal.,2014).

ThesuccessofPenicilliumstrainsismainlyduetotheir

occur-renceinvariousfoodandfeedstuffs(Santinietal.,2014),indoor

environmentssuchasair,dustanddampbuildingmaterials(Chang

etal.,1995;Scottetal.,2004;McMullinetal.,2014;Visagieetal.,

2014), as wellas in the marine (Gong et al., 2014; Kim et al.,

2014;Liaoetal.,2014;Quangetal.,2014;Guoetal.,2015;Park etal.,2015)andsoil(Leitãoetal.,2007; Alyet al.,2011;Gong et al., 2014; Moore-Kucera et al., 2014; Tansakul et al., 2014)

environments.Moreover,thecataboliccapacityofthese

microor-ganismsduetotherelativeunspeciﬁcityoftheirenzymestogether

withtheirlimited growth requirements, diversity of secondary

metabolitesproductionandhighabilitytoformextendedmycelial

networksallowthemtosurviveinaninhospitableenvironment.

It hasbeensuggested thattheproducts originatedfromfungal

metabolicmachinerysupply themwitha chemicalarsenal that

increases itsﬁtness under challenging ecological conditions. In

fact, these characteristics are shared by several fungal species

and couldbea seriousadvantage interms ofnatural selection.

Ontheotherhand,symbioticinteractionswithotherorganisms

co-occuringinthesamehabitathaveasigniﬁcantimpactinthe

ecosystem.Forinstance,itisknownthatPenicilliumspeciesare

importantphosphate-solubilizingmicroorganisms; this capacity

allowedPenicilliumoxalicumI1topromote maizegrowthwhen

funguswasinoculatedintheplant(Gongetal.,2014).

SomePenicilliumspeciesareconsideredtobeplantpathogens

duetotheircapacitytopotentiallyproducemycotoxinsthatare

then consumed by humans and animals. For instance,

Penicil-liumexpansum,PenicilliumitalicumandPenicilliumdigitatum,major

postharvestpathogens ofpomeandcitrus, producethe

polyke-tidelactone,namelypatulin(Lietal.,2015);howeverpatulinis

notrequiredbyP.expansumtosuccessfullyinfectapples(Ballester

etal.,2015;Lietal.,2015).Interesting,cell-freeﬁltrateof

Penicil-liumGP15-1increasedsystemicresistanceagainstcucumberleaf

infectionby theanthracnose pathogenColletotrichum orbiculare

(Hossainetal.,2014).OtherexampleisthepenicisteroidAisolated

from the culture extracts of the Penicillium chrysogenum

QEN-24Sstrainthatcolonizesanunidentiﬁedmarineredalgalspecies

belonging to the genus Laurencia. This polyoxygenated steroid

showedmoderateantifungalactivityagainstAlternariabrassicae

and potent activity against Aspergillus niger (Gao et al., 2011).

Recently,astudyconductedwithaP.janthinellumstrainshowed

thatitsinoculationintolerantSolanumlycopersicumreduced

cel-lularsuperoxideanionsinaluminumstress(Khanetal.,2015c).

Additionally,theeffectoffungalstraininthetomatoplantwas

com-paredtoexogenousgibberellicacidandasimilarbio-prospective

potentialwasdescribed.Basedontheseresults,theapplicationof

biochemicallyactiveendophyte wasproposedtoincreasemetal

phytoextractionandensurecropphysiologicalhomeostasis.

5. Salinestress,gibberellinsandPenicillium

5.1. Salinity

Salinityisthewordthatdescribessoilsthatenclosehigh

concen-trationsofwater-solublesalts,mainlyNaCl,whichcausingserious

agriculturalyieldlosses.Itisestimatedthat20%oftheworld’s

cul-tivatedﬁeldsandapproximatelyhalfofthearablesoilareaffected

bysalinity(SairamandTyagi,2004).Ifweconsiderthatin2050

thepopulationwillincrease2.3billion,representinganincreaseof

70%offoodcropproductiondemandsanewapproachfor

threat-eningfoodsecurityworldwideis essential(FAO, 2009).Salinity

is hostiletomost formsof life becauseit is responsiblefor an

imbalanceof cellularion homeostasis,which requiresa quickly

osmoticadjustmentviamorphologicalﬂexibilityandbiosynthesis

ofsecondarymetabolitessuchascompatiblesolutes,which

accu-mulationinplantsatthemillimolarrangeplayanimportantrole

inplanttolerancetosaltstress(ChenandMurata,2011;Nounjan

etal.,2012).Despitethat,theabilityofPenicilliumstrainstotolerate

highconcentrationsofNaClisknown.Infact,thegeneraPenicillium

isrepresentativeofthepan-globalstablemycobiotainhypersaline

environment(Butinaretal.,2011).

In plantshighsalinityinhibitsthegrowthof rootand shoot

systemsbylimitingtheavailabilityofwaterandmicronutrients

causingcellulardamageandmodulatingseveralprocesses.Besides

thegreateffortcanalizedtothecompatiblesolutes(forexample

betaine(Gaoetal.,2004),glycinebetaine(ChenandMurata,2011),

trehalose(Nounjanetal.,2012)andproline(Strizhovetal.,1997;

Nounjan et al.,2012)), phytohormone(abscisic acid(ABA),

jas-monate(JA),brassinosteroid(BR)andgibberellicacid(GA)(Geng

etal.,2013;Ismailetal.,2014;JulkowskaandTesterink,2015))

and enzymes(as ascorbate peroxidase, glutathione peroxidase,

catalase,polyphenoloxidase(Sofoetal.,2015))biosynthesis,the

salinityhasadditionalnegativeeffectsonthecellularenergy

sup-ply, photosynthesis and redox homeostasis, since plants must

assimilate Na+ _and _Cl− ₍_Zhu _et _al., _2010; _Jacoby _et _al., _2011;

Mulleretal.,2014).Whenplantsareundersalinityconditions,the

decreaseinphotosynthesiscanbemainlyattributedtolowerCO2

availabilitythroughstomatalclosure,beingthecontrolof

respira-tionratesdependonsubstratesupplyandbiochemicalregulation.

Itissuggestedthatthevariabilityinrespiratoryresponsesmayvary

signiﬁcantlybetweenspecies(Jacobyetal.,2011).

Theinﬂuxofsodiumionsbyrootepidermalandcorticalcells

through nonselectivecation channels (NSCCS) induces

depolar-ization of theplasma membrane, reducing potassium ions(K+₎

channels uptake through inward-rectifying (Shabala and Cuin,

2008).To preventadditional inﬂux of sodiumions two

deacti-vationmechanismsmaybeinvolved:byNSCCchannelsthrough

cAMP/cGMP-dependent signals or by high afﬁnity potassium

transporter(HKAT)channel.Asaconsequenceofosmoticstress,

activationofmechanosensitivecalciumchannelsresultsinan

addi-tionalinﬂuxofprotonsandcalciumions(Ismailetal.,2014).The

cytosolicconcentrationofcalcium(Ca2+₎_increase_inducing_reactive

oxygenspecies(ROS)productionthroughNADPHoxidase

stimula-tionandactivatingCa2+_{calmodulim-dependent}_kinases._The_Ca2+

calmodulim-dependentkinasesstimulatestheplasma-membrane

H+_-ATPases_activity_among_others_enzymes,_restoring_membrane

voltageandinhibitingdepolarization-activatedNSCCS(Klobusand

Janicka-Russak, 2004; Shabala et al., 2006; Ismail et al., 2014; JulkowskaandTesterink,2015).Ontheotherhand,Ca2+_and_ROS

modulatesthereleaseofabscisicacid(ABA),aphytohormonethat

regulatesseveralplantbiologicalprocessessuchasgrowth,

biosyn-thesisofcompatiblesolutes,controlofstomatalclosure,among

others(Ismailetal.,2014).

Inarecentandveryinterestingreview,itwasproposedthat

dependingonthetimingoftheeventstriggeredbythesodiumion

anadaptive/acclimationresponsesorthesodiumaccumulationin

thecytoplasmmightoccur.Theadaptiveresponsescouldinvolve

mechanismsofsequestrationintovacuoleandextrusionofsodium

aswellastheconstraintofjasmonate(JA)signalling.Meanwhile,a

delayintheactivationand,consequently,alsointhedeactivation,

of“salinitysignalling”throughthegenerationanddissipationof

triggeredcalcium-dependentsignalrelativetoasignaltransmitted

byROSwilloriginatetheactivationofJAsignalingandthusleading

tocelldeath(Ismailetal.,2014).

Itisoutofthescopeofthisreviewtodescribetheplant

cellu-larmechanismsandmolecularresponsestohighsalinity,butfor

thosereaderswhoareinterestedinthisaspectwerecommendthe

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Table1

GibberellinsproductionbyPenicilliumstrainsandeffectonplantgrowthundersalinitystress.

Penicilliumstrain Gibberellin(GA) Plantgrowtheffectundersalinitystress References P.citrinumKACC43900 GA11.95ng/ml CanpromoteIxerisrepensgrowth(shoot

length,plantlength)

Khanetal.(2008) GA33.83ng/ml GA46.03ng/ml GA50.365ng/ml GA72.35ng/ml GA90.65ng/ml GA120.11ng/ml GA150.72ng/ml GA190.67ng/ml GA200.30ng/ml GA241.40ng/ml

P.funiculosumLHL06 GA11.53ng/ml Canpromotesoybeangrowth(shootlength, shootfresh/drybiomass,chlorophyllcontent, photosynthesisrate,leafarea)

Khanetal.(2011a)

GA49.34ng/ml GA81.21ng/ml GA937.87ng/ml

P.minioluteumLHL09 GA412.84ng/ml Canpromotesoybeangrowth(shootlength, shootfresh/drybiomass,chlorophyllcontent, leafarea)

Khanetal.(2011b)

GA748.912ng/ml

Penicilliumsp.SJ-2-2 GA11.185ng/ml Canpromotecucumbergrowth(shootlength, plantheight,chlorophyllcontent,leafarea)

Youetal.(2012) GA31.255ng/ml GA43.497ng/ml GA71.357ng/ml GA90.530ng/ml GA120.335ng/ml GA190.011ng/ml GA200.033ng/ml GA240.838ng/ml GA340.049ng/ml

Penicilliumsp.LWL3 GA15.33ng/ml Canpromotesitiensgrowth(shootlength, shootfreshbiomass,photosynthesisrate)

Waqasetal.(2012) GA33.42ng/ml

P.janthinellumLK5 GA31.2ng/ml Khanetal.(2013a,b)

GA410.19ng/ml GA70.71ng/ml GA1213.98ng/ml

P.resedanumLK6 GA17.1ng/ml Canpromotepeppergrowth(shootlength, shootdryweight,photosynthesisrate)

Khanetal.(2015a,b,c) GA313.9ng/ml GA419.159ng/ml GA71.12ng/ml GA92.2ng/ml GA121.93ng/ml GA201.68ng/ml

Tyagi,2004;Ismailetal.,2014;Julkowskaand Testerink,2015).

Despite ofplant salinitystress researchadvancesin the recent

years,anunderstandingofthetemporaldynamicnatureof

tran-scriptionaleventsisstilllacking.Gibberellinsareanexampleof

classicalgrowthpromotinghormone;however,saltstressinduced

repressionofthegibberellinsignalingpathwaysresultinginlower

cellcycle(Westetal.,2004).GAbiosynthesisandsignalinghave

recentlybeenshowntobenecessaryduringthelatephasesofthe

saltresponsetopromoterecovery(Gengetal.,2013).Therefore,GA

presenceisalsoacriticalfactorundersaltstress,justifyingan

alter-nativeapproachtopreventitsabsence.Cansymbioticinteraction

plant-fungussupplygibberellins?

5.2. InteractionsbetweenPenicilliumandplantsthrough

gibberellins

Although various Penicillium species have been reported as

endophytics(SpurrandWelty,1975;Colladoetal.,1999;Larran

etal.,2001;Caoetal.,2002;Petersonetal.,2005),earlierthan2008

verylittlewasknownaboutthesesymptomlessmicroorganisms

livinginsidehostplantandgibberellinsproductionunder

salin-itystress.AstrainofPenicilliumcitrinumisolatedfromduneplant

Ixerisrepeneswasdescribedfortheﬁrsttimeasapossible

advan-tageforplantsatsalineenvironment(Khanetal.,2009).P.citrinum

KACC43900promotedI.repenesgrowthbytheproductionof

bioac-tivegibberellinsintherhizosphere(Khanetal.,2009).Later,several

studieswithdifferentPenicilliumstrainshavebeenreportedusing

alowgibberellinsbiosynthesis mutantricecultivar,Waito-Cfor

plantgrowth-promotingveriﬁcation.Waito-CisaGA-deﬁcientrice

mutant,whichlacksGA3␤-hydroxylase,andconsequentlyis

hin-deringGA1synthesisfromGA20(Ahmadetal.,2010).Inallofthese

studieswereconﬁrmedthatfungalstrainssuppliedplantgrowth

promotiontoWaito-C.InthecaseofPenicilliumfuniculosumLHL06

andPenicilliumminioluteumLHL09,isolatedfromGlycinemax.L.,

stimulatedWaito-Cgrowthbysecretionofbioactivegibberellins.

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Table2

PutativegibberellinbiosyntheticenzymesidentiﬁedbyhomologywiththeproteinsfromF.fujikuroi.

Species Putativegibberellinbiosyntheticenzyme Mycocosm ProteinID

Hitlenght %Identity E-value PenicilliumbilaiaeATCC20851v1.0 Ent-kaureneoxidase(P450-4) Penbi1|369049 163 34.90% 6.72E-65

CPS-KSEnt-kaur-16-enesynthase(CPS/KS) Penbi1|369053 243 40.30% 8.86E-107 CytochromeP450monooxygenase(P450-3) Penbi1|375870 110 35.37% 3.89E-51

GA14-synthase(P450-1) Penbi1|375870 150 41.10% 3.95E-74

GA20oxidase(P450-2) Penbi1|375870 150 42.25% 8.78E-78

Geranylgeranyldiphosphatesynthase(ggs2) Penbi1|416244 90 48.13% 4.96E-53

GA4desaturase(des) Penbi1|481848 36 39.56% 5.69E-09

PenicilliumfellutanumATCC48694v1.0 Ent-kaureneoxidase(P450-4) Penfe1|374742 103 34.33% 9.80E-47 CPS-KSEnt-kaur-16-enesynthase(CPS/KS) Penfe1|374742 113 35.42% 1.72E-54 CytochromeP450monooxygenase(P450-3) Penfe1|403578 171 45.72% 3.95E-81

GA14-synthase(P450-1) Penfe1|403578 82 41.84% 1.35E-50

GA20oxidase(P450-2) Penfe1|417921 47 43.12% 1.76E-12

Geranylgeranyldiphosphatesynthase(ggs2) Penfe1|424093 216 42.27% 7.29E-72

GA4desaturase(des) Penfe1|424093 172 42.57% 1.12E-90

PenicilliumglabrumDAOM239074v1.0 Ent-kaureneoxidase(P450-4) Pengl1|107178 112 37.46% 6.11E-52 CPS-KSEnt-kaur-16-enesynthase(CPS/KS) Pengl1|107178 144 42.99% 3.76E-76 CytochromeP450monooxygenase(P450-3) Pengl1|345507 96 47.76% 3.36E-60

GA14-synthase(P450-1) Pengl1|374226 64 38.55% 7.71E-16

GA20oxidase(P450-2) Pengl1|400029 126 40.38% 8.45E-60

Geranylgeranyldiphosphatesynthase(ggs2) Pengl1|401725 142 36.79% 3.39E-62

GA4desaturase(des) Pengl1|436008 177 39.51% 6.39E-71

PenicilliumjanthinellumATCC10455v1.0 Ent-kaureneoxidase(P450-4) Penja1|284697 35 34.65% 1.46E-07 CPS-KSEnt-kaur-16-enesynthase(CPS/KS) Penja1|427667 154 45.16% 1.99E-82 CytochromeP450monooxygenase(P450-3) Penja1|427667 149 43.44% 4.65E-88

GA14-synthase(P450-1) Penja1|434515 115 44.92% 4.97E-54

GA20oxidase(P450-2) Penja1|445613 203 45.62% 9.72E-84

Geranylgeranyldiphosphatesynthase(ggs2) Penja1|447197 145 37.56% 6.09E-60

GA4desaturase(des) Penja1|459586 87 48.07% 2.11E-46

PenicilliumraistrickiiATCC10490v1.0 Ent-kaureneoxidase(P450-4) Penra1|287118 191 43.51% 8.32E-115 CPS-KSEnt-kaur-16-enesynthase(CPS/KS) Penra1|287118 171 40.05% 2.71E-110 CytochromeP450monooxygenase(P450-3) Penra1|348500 99 37.79% 2.87E-48

GA14-synthase(P450-1) Penra1|352910 139 34.32% 1.17E-57

GA20oxidase(P450-2) Penra1|355675 83 41.50% 1.06E-26

Geranylgeranyldiphosphatesynthase(ggs2) Penra1|363110 112 47.66% 3.51E-58

GA4desaturase(des) Penra1|376286 194 35.93% 1.57E-60

GA4andGA7weredetected,respectively,showingthecapacityof thesestrainstoproducebioactivegibberellinsundersalinitystress (Ahmadetal.,2010;Khanetal.,2011c).Inanotherreportan

endo-phyticfungus,Penicilliumsp.LWL3,wasisolatedfromrootsofﬁeld

growncucumberplantsandsecretedGA1andGA3(Waqasetal.,

2012).Bioactivegibberellins,GA3,GA4andGA7,wereisolatedfrom

P.janthinellumLK5,anendophyticfungusinhabitingtherootsofS.

lycopersicumMill(tomatoplant)fromﬁeldslocatednear

Kyung-pookNationalUniversity.P.janthinellumLK5improvesgrowthof

Waito-C,aswellasofABA-deﬁcienttomateundersalinity,

reduc-ingsodiumiontoxicityandincrementingcalciumcontentsinits

rootascomparedtocontrol(Khanetal.,2013b).Recently,ithas

beenreportedthatendophytescouldhaveeffectscomparableto

thoseofexogenousgibberellins.WhentheendophyticP.resedanum

LK6,isolatedfromCapsicumannuumL.,andexogenousgibberellic

acidtreatmentswereappliedonpepperplantssigniﬁcantly

ame-lioratedthenegativeeffectofsalt stress.Ahigherbeneﬁteffect

wasobservedbyapplicationofcombinedLK6strainplus

gibberel-licacidtreatment.Moreover,italsoshowedthatLK6strainhadthe

abilitytoincreasebiomass,shootlength,chlorophyllcontentand

photosynthesisratecomparedwiththeuninfectedcontrolunder

salinitystress,suchasoccurredinotherPenicilliumstrains(Table1)

(Khanetal.,2015b).However,theprocessbywhichthese

phyto-hormonesaresecretedintoplanttissuesisnotknown(Khanetal.,

2015c).

Comparative study on gibberellins production of Fusarium

fujikuroi and Penicillium sp., curiously revealed that Penicillium

strainscapacity isgenerally similarorhigher than wildtype F.

fujikuroi.Early,ithasbeenreportedthatbioactiveGAproduction

capacityofaP.citrinumstrainwasmuchhigherthanF.fujikuroi

(Khanetal.,2008).ThePenicilliumsp.SJ-2-2,ahalophyteofhealthy

rootscollectedfromasaltmarshofSuncheonBayinSouthKorea,

synthesizedasmuchGA1andGA3thanF.fujikuroi,and

synthe-sizedmuchmoreofGA4andGA7(Youetal.,2012).Similarly,the

P.resedanumLK6wasalsoreportedtoproducesigniﬁcantlyhigher

amountsofGA1andGA4thantheF.fujifuroi,andGA3contentwas

atlowerlevel(Khanetal.,2015a).

Ithasbeenreportedthatplantsreacttomycorrhizationby

GAs-secretingPenicilliumstrains,alteringtheABA,JAandsalicylicacid

levels,aswellastheaccumulationofisoﬂavonesandtheenzymes

activitiesinvolvedintheremovalofROS,catalasesandperoxidases.

Additionally,endophytetreatmentimproveplantnutritionbalance

asaconsequenceofhighernitrogenandphosphorussolubilization

andK+_,_Mg2+_and_Ca2+_levels,_which_in_turn_might_{limit/inhibit}_the

uptakeofNa+_._Despite_of_antagonistic_behavior_described_in_the

lit-eratureinwhatconcerntoJA,ABAandenzymes,whichneedsto

beclariﬁedat“omics”levels,endophyticassociationhasnotonly

re-programmedtheplantforhighergrowthbutalsosigniﬁcantly

amelioratedtheeffectofsaltinducedstress(Khanetal.,2011a;

Khanetal.,2011b;Waqasetal.,2012;Khanetal.,2013a).The

mech-anismbywhichendophytetreatmentaugmentshostresponseto

salinitystressisstillnotclearlyunderstood(Khanetal.,2015a).

5.3. PutativegibberellinbiosyntheticgenesinPenicillium

InF.fujikuroigenomethegenesinvolvedinthemainstepsof

gibberellinbiosynthesisareclusteredtogether(Linnemannstons

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com-posed by seven genes: four genes encoding cytochrome P450

oxidoreductases(namedfrom1to4)involvedindifferent

hydrox-ylationstepsofthegibberellinnucleus,twoGGDPsynthasegenes

locatedintandem(Ent-kaur-16-enesynthase,CPS/KS,and

geranyl-geranyldiphosphatesynthase,ggs2),andaGA4desaturasegene

(des),encodingtheenzyme which convertsGA4 toGA7.

Avail-ablegenomicdatafromJGIMycocosmgenomicresource(Grigoriev

etal.,2014)allowedustolocalizeputativegibberellinbiosynthetic

genesin5outofthe14availablecompletegenomesbelongingto

thePenicilliumgenus(Table2).Interestingly,oneoftheanalyzed

genomesbelongstoP.janthinellumwhichhasbeenpreviously

char-acterizedasagibberellinproducer(Khanetal.,2013;KhanandLee,

2013).Thesequencehomologyoftheputativegibberellin

biosyn-theticenzymesindifferentPenicillium speciesshoweda higher

degreeofhomologyinthegroupofthecytochromeP450enzymes,

astheent-kaureneoxidase(P450-4)andtheGA14-synthase

(P450-1)(Fig.3).AlsoasdepictedinTable2,putativeCPS/KSproteinsfrom

differentPenicilliumspeciesshowedahighhomologywiththe

orig-inalenzymefromF.fujikuroi,whereasthedesaturaseenzymes(des)

arecomparativelylessconserved.

6. Conclusionsandfutureperspectives

Thereisincreasinginterestinthediscoveryofnaturally

occur-ring chemical molecules for stimulating plant growthin order

toincreaseagriculturalcropsyield.Endophyticfungiarewidely

foundinalmostallkindsofplants,andtheirspeciescomposition

andnumberseemstobeaffectedbyagesofplantsand

environ-mentalamongotherfactors.FungilikePenicilliumspeciescanbe

usedasa readilyrenewable and inexhaustiblesourceof

extro-litecompoundsthatcanimproveplantsundernegativebioticas

wellasabioticconditions.Itisnowcommonlyacceptedthatthis

phenomenonisobservedwhenendophyticfungi-plantsareunder

salinestress.Inthisenvironmentalconditiongibberellinsare

pro-ducedbyPenicilliumstrains.StructuresGA1,GA3,GA4andGA7

havebeenidentiﬁedwithfunctionasgrowthhormonesproduced

byPenicilliumstrainsassalinitystressresistanceresponse.

Inter-esting,therhizobacteriumPseudomonasputidaH-2-3isalsoableto

secretegibberellinwhensoybeanisundersalineanddroughtstress

conditions,improvingtheplantgrowth(Kangetal.,2014).Onthe

otherhand,ithasbeenshownthatplantsreducegibberellins

pro-ductionintheresponsetoabioticstress,reducinggrowthinorder

thatplantcanfocusitsenergyandcarbonresourcesonresisting

thestress(Colebrooketal.,2014).Ifwe consideredthat all

liv-ingorganismhaveasprioritygrowthandsurvival,thecapacityof

microorganismstoproducemetabolitesthatareplantsecondary

metabolitescouldbeawaythatmicroorganismsfoundto

embar-rassthehostplants?. Endophytic Penicilliumstrainsdrawfrom

plantthewater,foodandphysicalprotectionagainstbioticand

abi-oticadverseconditions,whichallowthemtolivewithintheplant

hoppingbyfavorableconditionstocompletelycolonizethe

host-plant.Meanwhile,endophyticsymbiosisresultedinsigniﬁcantly

higherassimilationofnutrientlikephosphorus,sulfur,magnesium,

calciumandpotassiumascomparedtocontrolplants;besides

sec-ondarymetabolitesthatendophytemayproduce.Ithasbeenalso

reportedthatendophyticfungibiomasscouldconstitutean

inter-estingnitrogensourceforplant.Furthermore,severalPenicillium

culturesrevealedthepresenceofindoleaceticacid,otherimportant

phytohormone (Khan et al., 2011b; Waqas et al., 2012).

Addi-tionally,itwasdescribedthatPenicilliumendophytescanhelped

planttore-programits responsestosalinestressbyregulating

theendogenousphytohormonesandenzymestominimizecellular

toxicity(Khanetal.,2013a;Khanetal.,2015c).Suchinteractions

betweennativeendophyticfungiandplanthostcouldbea

reli-ablemethodologytotheplantsaltstress,sincechemicalsolutions

couldbeharmfultoorganismsinthesoil,reducingthe

biodiver-sityofecosystems.Themajorconcernistopredictenvironmental

changes,endophyte-hostinteractions,aswellasplant-microﬂora

systemdevelopment.Nevertheless,webelievethatapplicationof

bioactivegibberellins Penicilliumstrainsproducers isa promise

environmentalfriendlystrategy of improvingplantgrowthand

amelioratingdamagecausebysaltstressincultivationcrops.

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