Ferritin-like family proteins in the anaerobe Bacteroides fragilis: when an oxygen storm is coming, take your iron to the shelter

Abstract

Bacteroides are gram-negative anaerobes and one of the most abundant members the lower GI tract microflora where they play an important role in normal intestinal physiology. Disruption of this commensal relationship has a great impact on human health and disease. Bacteroides spp. are significant opportunistic pathogens causing infections when the mucosal barrier integrity is disrupted following predisposing conditions such as GI surgery, perforated or gangrenous appendicitis, perforated ulcer, diverticulitis, trauma and inflammatory bowel diseases. B. fragilis accounts for 60–90 % of all anaerobic infections despite being a minor component of the genus (<1 % of the flora). Clinical strains of B. fragilis are among the most aerotolerant anaerobes. When shifted from anaerobic to aerobic conditions B. fragilis responds to oxidative stress by inducing the expression of an extensive set of genes involved in protection against oxygen derived radicals and iron homeostasis. In Bacteroides, little is known about the metal/oxidative stress interactions and the mobilization of intra-cellular non-heme iron during the oxidative stress response has been largely overlooked. Here we present an overview of the work carried out to demonstrate that both oxygen-detoxifying enzymes and iron-storage proteins are essential for B. fragilis to survive an adverse oxygen-rich environment. Some species of Bacteroides have acquired multiple homologues of the iron storage and detoxifying ferritin-like proteins but some species contain none. The proteins found in Bacteroides are classical mammalian H-type non-heme ferritin (FtnA), non-specific DNA binding and starvation protein (Dps) and the newly characterized bacterial Dps-Like miniferritin protein. The full contribution of ferritin-like proteins to pathophysiology of commensal and opportunistic pathogen Bacteroides spp. still remains to be elucidated.

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

“…In conclusion, this study shows that Bacteroides species assimilate Fe(III)‐xenosiderophores for growth under anaerobic conditions in vitro. Despite our limited knowledge of iron bound to xenosiderophores assimilation in anaerobes, our findings support previous studies demonstrating that Bacteroides have developed different strategies to deal with the challenges of iron acquisition, genetic regulation and iron‐storage during transitions from anaerobic to aerotolerant metabolism (Betteken, Rocha, & Smith, ; Gauss et al., ; Rocha & Smith, , , ). Moreover, future investigations on the transport and regulatory mechanisms for utilization of catechol siderophores in B. vulgatus associated with colitis will advance our understanding on the role iron acquisition systems play in Bacteroides pathophysiology.…”

An insider's perspective: Bacteroides as a window into the microbiome

“…For instance, many encode a cytochrome bd oxidase that is hypothesized to reduce intracellular oxygen levels, and by extension, gut oxygen levels, thereby permitting the growth of strict anaerobes that are otherwise killed by the presence of O 2 (ref. 31–33 ). This ability to tolerate and reduce oxygen levels would likely aid Bacteroides in spreading to new hosts and is perhaps a major reason why they are so widespread among mammals 21,34,35 .…”

“…While the nomenclature of those early days differed from that of today (the type species for Bacteroides , B. fragilis , was initially named ‘ Bacillus fragilis ’ in 1898 (ref. 20 ), and the genus name ‘ Bacteroides ’ was only coined two decades later 128 ), it stands to reason from more recent studies that the majority of those anaerobes were indeed members of the Bacteroides , with B. fragilis being the most prominent of the anaerobes and E. coli being the most prominent of the aerobes 33,123,129 . It is for this reason that B. fragilis has long been considered a human pathogen 130 .…”

Dps and DpsL Mediate SurvivalIn VitroandIn Vivoduring the Prolonged Oxidative Stress Response in Bacteroides fragilis

“…6 (see also Table S2 in the supplemental material) (40). For instance, Bacteroides vulgatus lacks dps but has the genes for DpsL and three ferritins.…”

“…Based on available genome sequences for B. fragilis (83 strains), Bacteroides uniformis (3 strains), Parabacteroides merdae (3 strains), Parabacteroides distasonis (8 strains), Bacteroides caccae (2 strains), Bacteroides ovatus (7 strains), B. vulgatus (8 strains), and B. thetaiotaomicron (3 strains), we observed that all strains of species possessing dps and dpsL homologues were consistent. With respect to conservation of the ferritins (ftnA), ftnA1 was conserved in all strains, but the presence of ftnA2 and ftnA3 was variable in strains of B. thetaiotaomicron, B. uniformis, and P. merdae (40). Because of the great diversity seen in the ferritin family proteins and the different responses to oxidative stress in these organisms, we wanted to ex- assays were performed in the rat tissue cage model.…”