Rocha Edson R, Krykunivsky Anna S
Department of Microbiology and Immunology, Brody School of Medicine, East Carolina University, Greenville, NC.
Intern from the Undergraduate Research Internship Placement Program, University of the West of England (UWE), Bristol, UK.
Microbiologyopen. 2017 Aug;6(4). doi: 10.1002/mbo3.479. Epub 2017 Apr 11.
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.
在本研究中，我们发现拟杆菌属物种在体外厌氧的铁限制条件下，利用铁（III）-异源铁载体作为外源铁的唯一来源来支持生长。脆弱拟杆菌是唯一能够利用铁（III）-高铁菌素的物种，而普通拟杆菌ATCC 8482和多形拟杆菌VPI 5482能够以剂量依赖的方式利用铁（III）-肠杆菌素和铁（III）-沙门菌素S4作为唯一的铁源。我们以脆弱拟杆菌同化铁（III）-高铁菌素的方式作为初始模型，来研究厌氧菌中异源铁载体的利用情况。脆弱拟杆菌含有两种外膜依赖TonB的转运蛋白（TBDTs），FchA1和FchA2，它们与大肠杆菌高铁菌素转运蛋白FhuA是同源物。fchA1基因的破坏在铁（III）-高铁菌素上仅产生部分生长缺陷，而fchA2突变体与亲本菌株相比没有生长缺陷。fchA1基因的遗传互补使生长恢复到亲本菌株水平，这表明它在铁（III）-高铁菌素同化中发挥作用，尽管我们不能排除转运系统中存在一些功能重叠，因为脆弱拟杆菌含有大量功能尚不清楚的TBDTs。然而，在feoAB突变体中，脆弱拟杆菌在铁（III）-高铁菌素上的生长被消除，这表明转运到周质空间的铁（III）-高铁菌素在通过FeoAB转运系统转运之前，在周质中释放亚铁的能力降低。此外，高铁菌素中铁的释放可能与硫醇氧化还原系统有关，因为trxB缺失突变体在铁（III）-高铁菌素存在下也无法生长。feoAB和trxB突变体的遗传互补完全恢复了在铁（III）-高铁菌素上的生长。综上所述，这些发现表明拟杆菌属物种已经形成了在厌氧生长条件下利用与异源铁载体结合的三价铁的机制，尽管在厌氧肠道环境中拟杆菌生物学中的调节和作用仍有待了解。
