Dual Zinc Transporter Systems in Vibrio cholerae Promote Competitive Advantages over Gut Microbiome

Zinc is an essential trace metal required for numerous cellular processes in all forms of life. In order to maintain zinc homeostasis, bacteria have developed several transport systems to regulate its uptake. In this study, we investigated zinc transport systems in the enteric pathogenVibrio cholerae, the causative agent of cholera. Bioinformatic analysis predicts that two gene clusters, VC2081 to VC2083 (annotated as zinc utilization genesznuABC) and VC2551 to VC2555 (annotated aszinc-regulatedgeneszrgABCDE), are regulated by the putative zinc uptake regulator Zur. Using promoter reporter and biochemical assays, we confirmed that Zur repressesznuABCandzrgABCDEpromoters in a Zn2+-dependent manner. Under Zn2+-limiting conditions, we found that mutations in either theznuABCorzrgABCDEgene cluster affect bacterial growth, withznuABCmutants displaying a more severe growth defect, suggesting that both ZnuABC and ZrgABCDE are involved in Zn2+uptake and that ZnuABC plays the predominant role. Furthermore, we reveal that ZnuABC and ZrgABCDE are important forV. choleraecolonization in both infant and adult mouse models, particularly in the presence of other intestinal microbiota. Collectively, our studies indicate that these two zinc transporter systems play vital roles in maintaining zinc homeostasis duringV. choleraegrowth and pathogenesis.

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The Yfe and Feo Transporters Are Involved in Microaerobic Growth and Virulence of Yersinia pestis in Bubonic Plague

Infection and Immunity ◽

10.1128/iai.00086-12 ◽

2012 ◽

Vol 80 (11) ◽

pp. 3880-3891 ◽

Cited By ~ 35

Author(s):

Jacqueline D. Fetherston ◽

Ildefonso Mier ◽

Helena Truszczynska ◽

Robert D. Perry

Keyword(s):

Yersinia Pestis ◽

Double Mutant ◽

Lethal Dose ◽

Growth Conditions ◽

Transport Systems ◽

Growth Defect ◽

Dependent Manner ◽

Bubonic Plague ◽

Pneumonic Plague ◽

Content Type

ABSTRACTThe Yfe/Sit and Feo transport systems are important for the growth of a variety of bacteria. InYersinia pestis, single mutations in eitheryfeorfeoresult in reduced growth under static (limited aeration), iron-chelated conditions, while ayfe feodouble mutant has a more severe growth defect. These growth defects were not observed when bacteria were grown under aerobic conditions or in strains capable of producing the siderophore yersiniabactin (Ybt) and the putative ferrous transporter FetMP. BothfetPand a downstream locus (flpforfetlinkedphenotype) were required for growth of ayfe feo ybtmutant under static, iron-limiting conditions. AnfeoBmutation alone had no effect on the virulence ofY. pestisin either bubonic or pneumonic plague models. Anfeo yfedouble mutant was still fully virulent in a pneumonic plague model but had an ∼90-fold increase in the 50% lethal dose (LD50) relative to the Yfe+Feo+parent strain in a bubonic plague model. Thus, Yfe and Feo, in addition to Ybt, play an important role in the progression of bubonic plague. Finally, we examined the factors affecting the expression of thefeooperon inY. pestis. Under static growth conditions, theY. pestis feo::lacZfusion was repressed by iron in a Fur-dependent manner but not in cells grown aerobically. Mutations infeoC,fnr,arcA,oxyR, orrstABhad no significant effect on transcription of theY. pestis feopromoter. Thus, the factor(s) that prevents repression by Fur under aerobic growth conditions remains to be identified.

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Interplay between the Zur Regulon Components and Metal Resistance inCupriavidus metallidurans

Journal of Bacteriology ◽

10.1128/jb.00192-19 ◽

2019 ◽

Vol 201 (15) ◽

Cited By ~ 2

Author(s):

Lucy Bütof ◽

Cornelia Große ◽

Hauke Lilie ◽

Martin Herzberg ◽

Dietrich H. Nies

Keyword(s):

Metal Resistance ◽

Zinc Homeostasis ◽

Transport Systems ◽

Starvation Response ◽

Content Type ◽

Resistance Factors ◽

Cupriavidus Metallidurans ◽

Dependent Protein ◽

Zinc Storage ◽

Physiological And Biochemical

ABSTRACTThe Zur regulon is central to zinc homeostasis in the zinc-resistant bacteriumCupriavidus metallidurans. It comprises the transcription regulator Zur, the zinc importer ZupT, and three members of the COG0523 family of metal-chaperoning G3E-type GTPases, annotated as CobW1, CobW2, and CobW3. The operon structures of thezurandcobW1loci were determined. To analyze the interplay between the Zur regulon components and metal resistance, deletion mutants were constructed from the wild-type strain CH34 and various other strains. The Zur regulon components interacted with the plasmid-encoded and chromosomally encoded metal resistance factors to acquire metals from complexes of EDTA and for homeostasis of and resistance to zinc, nickel, cobalt, and cadmium. The three G3E-type GTPases were characterized in more detail. CobW1 bound only 1 Zn atom per mol of protein with a stability constant slightly above that of 2-carboxy-2′-hydroxy-5′-sulfoformazylbenzene (Zincon) and an additional 0.5 Zn with low affinity. The CobW1 system was necessary to obtain metals from EDTA complexes. The GTPase CobW2 is a zinc storage compound and bound 0.5 to 1.5 Zn atoms tightly and up to 6 more with lower affinity. The presence of MgGTP unfolded the protein partially. CobW3 had no GTPase activity and equilibrated metal import by ZupT with that of the other metal transport systems. It sequestered 8 Zn atoms per mol with decreasing affinity. The three CobWs bound to the metal-dependent protein FolEIB2, which is encoded directly downstream ofcobW1. This demonstrated an important contribution of the Zur regulon components to metal homeostasis inC. metallidurans.IMPORTANCEZinc is an important transition metal cation and is present as an essential component in many enzymes, such as RNA polymerase. As with other transition metals, zinc is also toxic at higher concentrations so that living cells have to maintain strict control of their zinc homeostasis. Members of the COG0523 family of metal-chaperoning GE3-type GTPases exist in archaea, bacteria, and eucaryotes, including humans, and they may be involved in delivery of zinc to thousands of different proteins. We used a combination of molecular, physiological, and biochemical methods to demonstrate the important but diverse functions of COG0523 proteins inC. metallidurans, which are produced as part of the Zur-controlled zinc starvation response in this bacterium.

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Heterologous Expression of a Cryptic Gene Cluster from Streptomyces leeuwenhoekii C34T Yields a Novel Lasso Peptide, Leepeptin

Applied and Environmental Microbiology ◽

10.1128/aem.01752-19 ◽

2019 ◽

Vol 85 (23) ◽

Cited By ~ 5

Author(s):

Juan Pablo Gomez-Escribano ◽

Jean Franco Castro ◽

Valeria Razmilic ◽

Scott A. Jarmusch ◽

Gerhard Saalbach ◽

...

Keyword(s):

Natural Products ◽

Heterologous Expression ◽

Streptomyces Coelicolor ◽

Gene Clusters ◽

Bioinformatic Analysis ◽

Growth Media ◽

Content Type ◽

Lasso Peptide ◽

Lasso Peptides ◽

New Family

ABSTRACT Analysis of the genome sequence of Streptomyces leeuwenhoekii C34T identified biosynthetic gene clusters (BGCs) for three different lasso peptides (Lp1, Lp2, and Lp3) which were not known to be made by the strain. Lasso peptides represent relatively new members of the RiPP (ribosomally synthesized and posttranslationally modified peptides) family of natural products and have not been extensively studied. Lp3, whose production could be detected in culture supernatants from S. leeuwenhoekii C34T and after heterologous expression of its BGC in Streptomyces coelicolor, is identical to the previously characterized chaxapeptin. Lp1, whose production could not be detected or achieved heterologously, appears to be identical to a recently identified member of the citrulassin family of lasso peptides. Since production of Lp2 by S. leeuwenhoekii C34T was not observed, its BGC was also expressed in S. coelicolor. The lasso peptide was isolated and its structure confirmed by mass spectrometry and nuclear magnetic resonance analyses, revealing a novel structure that appears to represent a new family of lasso peptides. IMPORTANCE Recent developments in genome sequencing combined with bioinformatic analysis have revealed that actinomycetes contain a plethora of unexpected BGCs and thus have the potential to produce many more natural products than previously thought. This reflects the inability to detect the production of these compounds under laboratory conditions, perhaps through the use of inappropriate growth media or the absence of the environmental cues required to elicit expression of the corresponding BGCs. One approach to overcoming this problem is to circumvent the regulatory mechanisms that control expression of the BGC in its natural host by deploying heterologous expression. The generally compact nature of lasso peptide BGCs makes them particularly amenable to this approach, and, in the example given here, analysis revealed a new member of the lasso peptide family of RiPPs. This approach should be readily applicable to other cryptic lasso peptide gene clusters and would also facilitate the design and production of nonnatural variants by changing the sequence encoding the core peptide, as has been achieved with other classes of RiPPs.

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Vibrio cholerae Requires the Type VI Secretion System Virulence Factor VasX To Kill Dictyostelium discoideum

Infection and Immunity ◽

10.1128/iai.01266-10 ◽

2011 ◽

Vol 79 (7) ◽

pp. 2941-2949 ◽

Cited By ~ 118

Author(s):

Sarah T. Miyata ◽

Maya Kitaoka ◽

Teresa M. Brooks ◽

Steven B. McAuley ◽

Stefan Pukatzki

Keyword(s):

Vibrio Cholerae ◽

Dictyostelium Discoideum ◽

Virulence Factor ◽

Membrane Lipids ◽

Gene Clusters ◽

Secretion System ◽

Type Vi Secretion System ◽

Content Type ◽

Enzymatic Function ◽

Type Vi Secretion

ABSTRACTThe type VI secretion system (T6SS) is recognized as an important virulence mechanism in several Gram-negative pathogens. InVibrio cholerae, the causative agent of the diarrheal disease cholera, a minimum of three gene clusters—one main cluster and two auxiliary clusters—are required to form a functional T6SS apparatus capable of conferring virulence toward eukaryotic and prokaryotic hosts. Despite an increasing understanding of the components that make up the T6SS apparatus, little is known about the regulation of these genes and the gene products delivered by this nanomachine. VasH is an important regulator of theV. choleraeT6SS. Here, we present evidence that VasH regulates the production of a newly identified protein, VasX, which in turn requires a functional T6SS for secretion. Deletion ofvasXdoes not affect export or enzymatic function of the structural T6SS proteins Hcp and VgrG-1, suggesting that VasX is dispensable for the assembly of the physical translocon complex. VasX localizes to the bacterial membrane and interacts with membrane lipids. We present VasX as a novel virulence factor of the T6SS, as aV. choleraemutant lackingvasXexhibits a phenotype of attenuated virulence towardDictyostelium discoideum.

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Vibrio cholerae VciB Mediates Iron Reduction

Journal of Bacteriology ◽

10.1128/jb.00874-16 ◽

2017 ◽

Vol 199 (12) ◽

Cited By ~ 6

Author(s):

Eric D. Peng ◽

Shelley M. Payne

Keyword(s):

Electron Transport ◽

Vibrio Cholerae ◽

Ferrous Iron ◽

Electron Transport Chain ◽

Iron Reduction ◽

Iron Transport ◽

Ferric Iron ◽

Transport Systems ◽

Content Type ◽

Transport Chain

ABSTRACT Vibrio cholerae is the causative agent of the severe diarrheal disease cholera. V. cholerae thrives within the human host, where it replicates to high numbers, but it also persists within the aquatic environments of ocean and brackish water. To survive within these nutritionally diverse environments, V. cholerae must encode the necessary tools to acquire the essential nutrient iron in all forms it may encounter. A prior study of systems involved in iron transport in V. cholerae revealed the existence of vciB, which, while unable to directly transport iron, stimulates the transport of iron through ferrous (Fe2+) iron transport systems. We demonstrate here a role for VciB in V. cholerae in which VciB stimulates the reduction of Fe3+ to Fe2+, which can be subsequently transported into the cell with the ferrous iron transporter Feo. Iron reduction is independent of functional iron transport but is associated with the electron transport chain. Comparative analysis of VciB orthologs suggests a similar role for other proteins in the VciB family. Our data indicate that VciB is a dimer located in the inner membrane with three transmembrane segments and a large periplasmic loop. Directed mutagenesis of the protein reveals two highly conserved histidine residues required for function. Taken together, our results support a model whereby VciB reduces ferric iron using energy from the electron transport chain. IMPORTANCE Vibrio cholerae is a prolific human pathogen and environmental organism. The acquisition of essential nutrients such as iron is critical for replication, and V. cholerae encodes a number of mechanisms to use iron from diverse environments. Here, we describe the V. cholerae protein VciB that increases the reduction of oxidized ferric iron (Fe3+) to the ferrous form (Fe2+), thus promoting iron acquisition through ferrous iron transporters. Analysis of VciB orthologs in Burkholderia and Aeromonas spp. suggest that they have a similar activity, allowing a functional assignment for this previously uncharacterized protein family. This study builds upon our understanding of proteins known to mediate iron reduction in bacteria.

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VpsR Directly Activates Transcription of Multiple Biofilm Genes in Vibrio cholerae

Journal of Bacteriology ◽

10.1128/jb.00234-20 ◽

2020 ◽

Vol 202 (18) ◽

Cited By ~ 2

Author(s):

Meng-Lun Hsieh ◽

Christopher M. Waters ◽

Deborah M. Hinton

Keyword(s):

Rna Polymerase ◽

Vibrio Cholerae ◽

Biofilm Formation ◽

Core Promoter ◽

Class Ii ◽

Class I ◽

Dependent Manner ◽

Mobility Shift ◽

Content Type

ABSTRACT Vibrio cholerae biofilm biogenesis, which is important for survival, dissemination, and persistence, requires multiple genes in the Vibrio polysaccharides (vps) operons I and II as well as the cluster of ribomatrix (rbm) genes. Transcriptional control of these genes is a complex process that requires several activators/repressors and the ubiquitous signaling molecule, cyclic di-GMP (c-di-GMP). Previously, we demonstrated that VpsR directly activates RNA polymerase containing σ70 (σ70-RNAP) at the vpsL promoter (PvpsL), which precedes the vps-II operon, in a c-di-GMP-dependent manner by stimulating formation of the transcriptionally active, open complex. Using in vitro transcription, electrophoretic mobility shift assays, and DNase I footprinting, we show here that VpsR also directly activates σ70-RNAP transcription from other promoters within the biofilm formation cluster, including PvpsU, at the beginning of the vps-I operon, PrbmA, at the start of the rbm cluster, and PrbmF, which lies upstream of the divergent rbmF and rbmE genes. In this capacity, we find that VpsR is able to behave both as a class II activator, which functions immediately adjacent/overlapping the core promoter sequence (PvpsL and PvpsU), and as a class I activator, which functions farther upstream (PrbmA and PrbmF). Because these promoters vary in VpsR-DNA binding affinity in the absence and presence of c-di-GMP, we speculate that VpsR’s mechanism of activation is dependent on both the concentration of VpsR and the level of c-di-GMP to increase transcription, resulting in finely tuned regulation. IMPORTANCE Vibrio cholerae, the bacterial pathogen that is responsible for the disease cholera, uses biofilms to aid in survival, dissemination, and persistence. VpsR, which directly senses the second messenger c-di-GMP, is a major regulator of this process. Together with c-di-GMP, VpsR directly activates transcription by RNA polymerase containing σ70 from the vpsL biofilm biogenesis promoter. Using biochemical methods, we demonstrate for the first time that VpsR/c-di-GMP directly activates σ70-RNA polymerase at the first genes of the vps and ribomatrix operons. In this regard, it functions as either a class I or class II activator. Our results broaden the mechanism of c-di-GMP-dependent transcription activation and the specific role of VpsR in biofilm formation.

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Discovery of Gene Cluster for Mycosporine-Like Amino Acid Biosynthesis from Actinomycetales Microorganisms and Production of a Novel Mycosporine-Like Amino Acid by Heterologous Expression

Applied and Environmental Microbiology ◽

10.1128/aem.00727-14 ◽

2014 ◽

Vol 80 (16) ◽

pp. 5028-5036 ◽

Cited By ~ 39

Author(s):

Kiyoko T. Miyamoto ◽

Mamoru Komatsu ◽

Haruo Ikeda

Keyword(s):

Amino Acid ◽

Gene Cluster ◽

Gene Clusters ◽

Biosynthetic Gene Cluster ◽

Dependent Manner ◽

Biosynthetic Gene ◽

Biosynthetic Gene Clusters ◽

Gram Positive ◽

Content Type ◽

Gram Positive Bacteria

ABSTRACTMycosporines and mycosporine-like amino acids (MAAs), including shinorine (mycosporine-glycine-serine) and porphyra-334 (mycosporine-glycine-threonine), are UV-absorbing compounds produced by cyanobacteria, fungi, and marine micro- and macroalgae. These MAAs have the ability to protect these organisms from damage by environmental UV radiation. Although no reports have described the production of MAAs and the corresponding genes involved in MAA biosynthesis from Gram-positive bacteria to date, genome mining of the Gram-positive bacterial database revealed that two microorganisms belonging to the orderActinomycetales,Actinosynnema mirumDSM 43827 andPseudonocardiasp. strain P1, possess a gene cluster homologous to the biosynthetic gene clusters identified from cyanobacteria. When the two strains were grown in liquid culture,Pseudonocardiasp. accumulated a very small amount of MAA-like compound in a medium-dependent manner, whereasA. mirumdid not produce MAAs under any culture conditions, indicating that the biosynthetic gene cluster ofA. mirumwas in a cryptic state in this microorganism. In order to characterize these biosynthetic gene clusters, each biosynthetic gene cluster was heterologously expressed in an engineered host,Streptomyces avermitilisSUKA22. Since the resultant transformants carrying the entire biosynthetic gene cluster controlled by an alternative promoter produced mainly shinorine, this is the first confirmation of a biosynthetic gene cluster for MAA from Gram-positive bacteria. Furthermore,S. avermitilisSUKA22 transformants carrying the biosynthetic gene cluster for MAA ofA. mirumaccumulated not only shinorine and porphyra-334 but also a novel MAA. Structure elucidation revealed that the novel MAA is mycosporine-glycine-alanine, which substitutesl-alanine for thel-serine of shinorine.

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Csr1/Zap1 Maintains Zinc Homeostasis and Influences Virulence in Candida dubliniensis but Is Not Coupled to Morphogenesis

Eukaryotic Cell ◽

10.1128/ec.00078-15 ◽

2015 ◽

Vol 14 (7) ◽

pp. 661-670 ◽

Cited By ~ 17

Author(s):

Bettina Böttcher ◽

Katja Palige ◽

Ilse D. Jacobsen ◽

Bernhard Hube ◽

Sascha Brunke

Keyword(s):

Living Organism ◽

Tube Formation ◽

Infection Process ◽

Candida Dubliniensis ◽

Zinc Homeostasis ◽

Growth Defect ◽

Infection Model ◽

Content Type ◽

Restricted Environment ◽

Embryonated Chicken

ABSTRACTThe supply and intracellular homeostasis of trace metals are essential for every living organism. Therefore, the struggle for micronutrients between a pathogen and its host is an important determinant in the infection process. In this work, we focus on the acquisition of zinc byCandida dubliniensis, an emerging pathogen closely related toCandida albicans. We show that the transcription factor Csr1 is essential forC. dubliniensisto regulate zinc uptake mechanisms under zinc limitation: it governs the expression of the zinc transporter genesZRT1,ZRT2, andZRT3and of the zincophore genePRA1. Exclusively, artificial overexpression ofZRT2partially rescued the growth defect of acsr1Δ/Δ mutant in a zinc-restricted environment. Importantly, we found that, in contrast to what is seen inC. albicans,Csr1(also calledZap1) is not a major regulator of dimorphism inC. dubliniensis. However, although acsr1Δ/Δ strain showed normal germ tube formation, we detected a clear attenuation in virulence using an embryonated chicken egg infection model. We conclude that, unlike inC. albicans, Csr1 seems to be a virulence factor ofC. dubliniensisthat is not coupled to filamentation but is strongly linked to zinc acquisition during pathogenesis.

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Glucose-Specific Enzyme IIA of the Phosphoenolpyruvate:Carbohydrate Phosphotransferase System Modulates Chitin Signaling Pathways in Vibrio cholerae

Journal of Bacteriology ◽

10.1128/jb.00127-17 ◽

2017 ◽

Vol 199 (18) ◽

Cited By ~ 5

Author(s):

Shouji Yamamoto ◽

Makoto Ohnishi

Keyword(s):

Gene Expression ◽

Signaling Pathways ◽

Vibrio Cholerae ◽

Nutrient Status ◽

Sensor Kinase ◽

Dependent Manner ◽

Specific Enzyme ◽

Phosphotransferase System ◽

Natural Competence ◽

Content Type

ABSTRACTInVibrio cholerae, the genes required for chitin utilization and natural competence are governed by the chitin-responsive two-component system (TCS) sensor kinase ChiS. In the classical TCS paradigm, a sensor kinase specifically phosphorylates a cognate response regulator to activate gene expression. However, our previous genetic study suggested that ChiS stimulates the non-TCS transcriptional regulator TfoS by using mechanisms distinct from classical phosphorylation reactions (S. Yamamoto, J. Mitobe, T. Ishikawa, S. N. Wai, M. Ohnishi, H. Watanabe, and H. Izumiya, Mol Microbiol 91:326–347, 2014,https://doi.org/10.1111/mmi.12462). TfoS specifically activates the transcription oftfoR, encoding a small regulatory RNA essential for competence gene expression. Whether ChiS and TfoS interact directly remains unknown. To determine if other factors mediate the communication between ChiS and TfoS, we isolated transposon mutants that turned offtfoR::lacZexpression but possessed intactchiSandtfoSgenes. We demonstrated an unexpected association of chitin-induced signaling pathways with the glucose-specific enzyme IIA (EIIAglc) of the phosphoenolpyruvate:carbohydrate phosphotransferase system (PTS) for carbohydrate uptake and catabolite control of gene expression. Genetic and physiological analyses revealed that dephosphorylated EIIAglcinactivated natural competence andtfoRtranscription. Chitin-induced expression of thechboperon, which is required for chitin transport and catabolism, was also repressed by dephosphorylated EIIAglc. Furthermore, the regulation oftfoRandchbexpression by EIIAglcwas dependent on ChiS and intracellular levels of ChiS were not affected by disruption of the gene encoding EIIAglc. These results define a previously unknown connection between the PTS and chitin signaling pathways inV. choleraeand suggest a strategy whereby this bacterium can physiologically adapt to the existing nutrient status.IMPORTANCEThe EIIAglcprotein of the PTS coordinates a wide variety of physiological functions with carbon availability. In this report, we describe an unexpected association of chitin-activated signaling pathways inV. choleraewith EIIAglc. The signaling pathways are governed by the chitin-responsive TCS sensor kinase ChiS and lead to the induction of chitin utilization and natural competence. We show that dephosphorylated EIIAglcinhibits both signaling pathways in a ChiS-dependent manner. This inhibition is different from classical catabolite repression that is caused by lowered levels of cyclic AMP. This work represents a newly identified connection between the PTS and chitin signaling pathways inV. choleraeand suggests a strategy whereby this bacterium can physiologically adapt to the existing nutrient status.

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Zinc Competition among the Intestinal Microbiota

mBio ◽

10.1128/mbio.00171-12 ◽

2012 ◽

Vol 3 (4) ◽

Cited By ~ 61

Author(s):

Lindsay M. Gielda ◽

Victor J. DiRita

Keyword(s):

Gastrointestinal Tract ◽

Campylobacter Jejuni ◽

Pathogenic Bacteria ◽

Zinc Transporter ◽

Zinc Uptake ◽

Zinc Binding ◽

Transport Systems ◽

Content Type ◽

High Affinity ◽

Wide Range

ABSTRACT Bioavailable levels of trace metals, such as iron and zinc, for bacterial growth in nature are sufficiently low that most microbes have evolved high-affinity binding and transport systems. The microbe Campylobacter jejuni lives in the gastrointestinal tract of chickens, the principal source of human infection. A high-affinity ABC transporter for zinc uptake is required for Campylobacter survival in chicken intestines in the presence of a normal microbiota but not when chickens are raised with a limited microbiota. Mass spectrometric analysis of cecal contents revealed the presence of numerous zinc-binding proteins in conventional chicks compared to the number in limited-microbiota chicks. The presence of a microbiota results in the production of host zinc-binding enzymes, causing a growth restriction for bacteria that lack the high-affinity zinc transporter. Such transporters in a wide range of pathogenic bacteria make them good targets for the development of broad-spectrum antimicrobials. IMPORTANCE Zinc is an essential trace element for the growth of most organisms. Quantities of zinc inside cells are highly regulated, as too little zinc does not support growth, while too much zinc is toxic. Numerous bacterial cells require zinc uptake systems for growth and virulence. The work presented here demonstrates that the microbiota in the gastrointestinal tract reduces the quantity of zinc. Without a high-affinity zinc transporter, Campylobacter jejuni, a commensal organism of chickens, is unable to replicate or colonize the gastrointestinal tract. This is the first demonstration of zinc competition between microbiota in the gastrointestinal tract of a host. These results could have profound implications in the field of microbial pathogenesis and in our understanding of host metabolism and the microbiota.

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