Research Article: T6SS: The bacterial “fight club” in the host gut

Date Published: June 8, 2017

Publisher: Public Library of Science

Author(s): Thibault G. Sana, Kyler A. Lugo, Denise M. Monack, Deborah A. Hogan.

http://doi.org/10.1371/journal.ppat.1006325

Abstract

Partial Text

The mammalian gut is home to a densely populated community of microorganisms that not only provide their host with nutritional benefits but also offer protection against foreign pathogens [1]. Since the gut is an environment limited in both space and nutrients, these microbes have evolved multiple mechanisms and strategies to either coexist or compete with other organisms that share the same resources. While some species will switch their metabolism to utilize secondary nutrients, others opt to take a more direct approach and directly kill their competitors by releasing chemical compounds or by secreting effectors via specific secretion systems [2] such as the type VI secretion system (T6SS).

To manipulate and control their local environment, bacteria often secrete proteins and effectors into the surrounding extracellular medium or directly into target cells using complex nanomachines called secretion systems. While these systems can vastly differ in function and composition, the T6SS is structurally homologous to a contractile T4 bacteriophage tail [9] and shares many evolutionarily conserved core components found in the T4 bacteriophages [3].

Once it was established that the T6SS can serve as an antibacterial weapon, researchers wondered whether this activity is important in modulating bacterial interactions in the mammalian gut. By studying the gut commensal bacterium Bacteroides fragilis, Wexler and colleagues determined that more than 109 T6SS-firing events occur per minute per gram of colonic contents, and that these microbial symbionts require their T6SS to persist in the gut [4]. Moreover, 130 T6SS loci were identified within the 205 human Bacteroidales genomes analyzed, suggesting that about a quarter of the human gut microbiota encode at least 1 T6SS [19] and that T6SS genetic elements may be transferable between Bacteroidales species [20]. Based on the dramatic firing rate and the large distribution of such machineries amongst gut commensals’ genomes, it is reasonable to hypothesize that T6SSs are key players involved in modulating ecological dynamics of the gut microbiota.

T6SSs are not limited to commensal bacteria. Many gram-negative enteric pathogens, including Vibrio cholerae, Campylobacter jejuni, Shigella flexneri, and Citrobacter rodentium, contain T6SSs. Moreover, both V. cholerae and C. rodentium utilize their T6SS to kill other bacteria in vitro [21–22]. In fact, in vitro studies have shown that the V. cholerae T6SS is activated by mucins and by microbiota-modified bile salt [23]. Consistent with these findings, an intact T6SS is required for V. cholerae colonization of the guts of infant rabbits [24].

The answer is “possibly.” Though there is much to be discovered, it may be possible to engineer probiotic commensal species that produce and use T6SSs that are designed to specifically kill certain enteric pathogens. Engineering such a commensal may come at a cost, however, depending on how specific the T6SS-dependent antibacterial response is. If the T6SS’s target isn’t specific enough, it may also kill resident gut bacteria that are important for maintaining homeostasis and thus negatively impact the health of the host.

In a way, yes, there is. It seems bacteria are secretly fighting amongst one another in the gut via their T6SSs. While much is yet to be discovered, T6SSs provide their host with protection against invading pathogens and may be responsible for dictating resident microbiota compositions. On the other hand, pathogens have figured out how to breach this defense mechanism, leading to their successful colonization of the mammalian gut.

 

Source:

http://doi.org/10.1371/journal.ppat.1006325

 

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