Effect of ferric and ferrous iron chelators on growth of Bacteroides fragilis under anaerobic conditions

Rocha, Edson R.

doi:10.1016/0378-1097(91)90393-o

Cited by 15 publications

(27 citation statements)

References 6 publications

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“…However, growth of B. vulgatus 40G2‐33 and 20‐15 can occur in the presence of heme if Fe(III)‐enterobactin (Figure b) or inorganic iron are provided exogenously (Figure a). In contrast, the control strains B. vulgatus 10–9 and 16–4 isolated from healthy individuals and B. fragilis grew on heme alone as expected (Figure c) since in the absence of exogenous iron, iron can be obtained from heme (Rocha et al., ; Sperry et al., ; Verweij‐Van Vught, Otto, Namavar, Sparrius, & Maclaren, ). It is important to mention that growth of Bacteroides species is not stimulated in media lacking heme or protoporhyrin IX (Rocha et al., ; Sperry et al., ; Verweij‐Van Vught et al., ).…”

Section: Resultsmentioning

confidence: 61%

Anaerobic utilization of Fe(III)‐xenosiderophores among Bacteroides species and the distinct assimilation of Fe(III)‐ferrichrome by Bacteroides fragilis within the genus

Rocha

Krykunivsky

2017

MicrobiologyOpen

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In this study, we show that Bacteroides species utilize Fe(III)‐xenosiderophores as the only source of exogenous iron to support growth under iron‐limiting conditions in vitro anaerobically. Bacteroides fragilis was the only species able to utilize Fe(III)‐ferrichrome while Bacteroides vulgatus ATCC 8482 and Bacteroides thetaiotaomicron VPI 5482 were able to utilize both Fe(III)‐enterobactin and Fe(III)‐salmochelin S4 as the only source of iron in a dose‐dependent manner. We have investigated the way B. fragilis assimilates Fe(III)‐ferrichrome as initial model to understand the utilization of xenosiderophores in anaerobes. B. fragilis contains two outer membrane TonB‐dependent transporters (TBDTs), FchA1 and FchA2, which are homologues to Escherichia coli ferrichrome transporter FhuA. The disruption of fchA1 gene had only partial growth defect on Fe(III)‐ferrichrome while the fchA2 mutant had no growth defect compared to the parent strain. The genetic complementation of fchA1 gene restored growth to parent strain levels indicating that it plays a role in Fe(III)‐ferrichrome assimilation though we cannot rule out some functional overlap in transport systems as B. fragilis contains abundant TBDTs whose functions are yet not understood. However, the growth of B. fragilis on Fe(III)‐ferrichrome was abolished in a feoAB mutant indicating that Fe(III)‐ferrichrome transported into the periplasmic space was reduced in the periplasm releasing ferrous iron prior to transport through the FeoAB transport system. Moreover, the release of iron from the ferrichrome may be linked to the thiol redox system as the trxB deletion mutant was also unable to grow in the presence of Fe(III)‐ferrichrome. The genetic complementation of feoAB and trxB mutants completely restored growth on Fe(III)‐ferrichrome. Taken together, these findings show that Bacteroides species have developed mechanisms to utilize ferric iron bound to xenosiderophores under anaerobic growth conditions though the regulation and role in the biology of Bacteroides in the anaerobic intestinal environment remain to be understood.

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Section: Resultsmentioning

confidence: 61%

Anaerobic utilization of Fe(III)‐xenosiderophores among Bacteroides species and the distinct assimilation of Fe(III)‐ferrichrome by Bacteroides fragilis within the genus

Rocha

Krykunivsky

2017

MicrobiologyOpen

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“…Several studies have shown that B. fragilis is unable to synthesize protoporphyrin macrocycle and has an essential requirement for heme and nonheme iron (31,45). This nutritional requirement correlates with the expression and role HlyBA might play to make possible bacterial access to iron and heme under the low-iron conditions encountered in host tissues.…”

Section: Discussionmentioning

confidence: 99%

Characterization ofBacteroides fragilisHemolysins and Regulation and Synergistic Interactions of HlyA and HlyB

et al. 2006

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This study describes the presence of 10 hemolysin orthologs in the genome of the opportunistic human anaerobic pathogen Bacteroides fragilis, which is currently classified as a nonhemolytic bacterium. The hemolysins were designated HlyA through HlyI plus HlyIII. All cloned hemolysin genes were able to confer hemolytic activity to a nonhemolytic Escherichia coli strain on blood agar plates. Interestingly, HlyH was found to be present in the genome of the B. fragilis NCTC9343 strain but absent in strains 638R, YCH46, and Bacteroides thetaiotaomicron VPI-5482. The hemolysins HlyA, HlyB, and HlyIII were selected for further characterization. HlyA, HlyB, and HlyIII were cytolytic to erythrocytes on liquid hemolytic assay. When hlyA and hlyB were expressed together in a nonhemolytic E. coli strain, the strain showed enhanced hemolytic activity on blood agar plates. Further analysis revealed that HlyA and HlyB have synergistic hemolytic activity as detected by the liquid hemolytic assay. In addition, the two-component hemolysins HlyA and HlyB form a protein-protein complex in vivo as determined by bacterial two-hybrid system assay. The hlyB and hlyA genes are organized in an operon that is coordinately regulated by iron and oxygen. Northern blot hybridization analysis revealed that hlyBA were expressed as a bicistronic mRNA induced approximately 2.5-fold under low-iron conditions and repressed in iron-rich medium. The normal ironregulated expression of hlyBA mRNA was lost in the furA mutant strain. In contrast, the hlyA gene was also expressed as a single mRNA in iron-rich medium, but its expression was reduced approximately threefold under low-iron conditions in a Fur-independent manner. This suggests that hlyA alone is regulated by an unidentified iron-dependent regulator. Moreover, the expression levels of hlyBA and hlyA were reduced about threefold following oxygen exposure and treatment with hydrogen peroxide. Taken together, these results suggest that iron and oxidative stress have an effect on the control of hlyBA and hlyA transcriptional levels. A hlyBA mutant was constructed, and its hemolytic activity was greatly diminished compared to those of the hlyIII mutant and parent strains. In addition, the hlyBA mutant had a significant modification in colony morphology and growth deficiency compared to the parent strain. The implications of these findings for the pathophysiology of B. fragilis in extraintestinal infections and competition in ecological systems for this organism are discussed.

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“…For example, several rodent and clinical studies as well as studies utilizing colonic fermentators demonstrated a reduction in Bacteroides and Roseburia that, to our knowledge, have not been reported to produce siderophores [91] [92] [93] [59] [81] [83] [87] [61]. Interestingly, low iron availability frequently corresponds with significant decreases in fecal concentrations of proprionate and butyrate, short chain fatty acids (SCFA) that are metabolic byproducts of microbial anaerobic fermentation [81] [86] [85] [87] [61] [90].…”

Section: Siderophores As Modulators Of Microbial Communitiesmentioning

confidence: 99%

Siderophore-mediated iron acquisition and modulation of host-bacterial interactions

Ellermann

Arthur

2017

Free Radical Biology and Medicine

124

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Iron is an essential micronutrient for most life forms including the majority of resident bacteria of the microbiota and their mammalian hosts. Bacteria have evolved numerous mechanisms to competitively acquire iron within host environments, such as the secretion of small molecules known as siderophores that can solubilize iron for bacterial use. However, siderophore biosynthesis and acquisition is not a capability equally harbored by all resident bacteria. Moreover, the structural diversity of siderophores creates variability in the susceptibility to host mechanisms that serve to counteract siderophore-mediated iron acquisition and limit bacterial growth. As a result, the differential capabilities to acquire iron among members of a complex microbial community carry important implications for the growth and function of resident bacteria. Siderophores can also directly influence host function by modulating cellular iron homeostasis, further providing a mechanism by which resident bacteria may influence their local environment at the host-microbial interface. This review will explore the putative mechanisms by which siderophore production by resident bacteria in the intestines may influence microbial community dynamics and host-bacterial interactions with important implications for pathogen- and microbiota-driven diseases including infection, inflammatory bowel diseases and colorectal cancer.

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Effect of ferric and ferrous iron chelators on growth of Bacteroides fragilis under anaerobic conditions

Cited by 15 publications

References 6 publications

Anaerobic utilization of Fe(III)‐xenosiderophores among Bacteroides species and the distinct assimilation of Fe(III)‐ferrichrome by Bacteroides fragilis within the genus

Anaerobic utilization of Fe(III)‐xenosiderophores among Bacteroides species and the distinct assimilation of Fe(III)‐ferrichrome by Bacteroides fragilis within the genus

Characterization ofBacteroides fragilisHemolysins and Regulation and Synergistic Interactions of HlyA and HlyB

Siderophore-mediated iron acquisition and modulation of host-bacterial interactions

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