Bacteriophage adhered to mucus provide a novel mucosal immune system (P3166)

Abstract

Mucosal surfaces serve as a primary entry point for multiple pathogens and are therefore principal sites of immune defense. Here we demonstrate through in vitro and in silico studies that increased phage adherence to the host mucosal layer, provides a novel immune defense mechanism. We show that compared to the surrounding environment, phage-to-bacteria ratios were increased on all mucosal surfaces sampled ranging from cnidarians to humans. This increased phage abundance protects the underlying epithelium from bacterial infection. Enrichment of phage on mucus occurs via interactions between host mucin glycoproteins and phage immunoglobulin-like protein domains exposed on phage capsids. Metagenomic analysis found these immunoglobulin-like proteins present in many environments, particularly those adjacent to mucosal surfaces. Preliminary glycan microarrays and 2D gel electrophoresis show that phage adherence can rapidly adapt to hosts mucus glycan profiles, and in response, the host may regulate its mucus glycosylation to select for a beneficial phage community. This adaptation between phage and host provide a mechanism for the manipulation and selection of the mucosal microbiota. Based on these observations, we present the Bacteriophage Adherence to Mucus (BAM) model describing a phage-derived mucosal immunity with potential applicability to all mucosal surfaces, thus opening a novel field of immunological study.

An extended catalog of integrated prophages in the infant and adult fecal microbiome shows high prevalence of lysogeny

“…Importantly, a similar prevalence of prophages was previously reported in the gut microbiota of a single adult individual, where the authors reported 72% of the MAGs derived from gut bacteria were lysogen (Sutcliffe et al, 2023) Similarly, a lysogen prevalence of 70% in MAGs derived from murine gut bacteria was reported (Kim and Bae, 2018). This high prevalence of lysogeny in gut microbiota is thought to contribute to phage-mediated immunity in the gut mucosal layer (Barr et al, 2013;Silveira and Rohwer, 2016). The Piggyback-the-Winner model suggests that lysogeny is the preferred lifestyle in dense and rapidly growing bacterial communities (Knowles et al, 2016;Brown et al, 2022).…”

Decolonization of asymptomatic carriage of multi-drug resistant bacteria by bacteriophages?

“…Also, in mice gut colonization experiments with E. coli or K. pneumoniae, even though the bacteria are mainly observed in the lumen, some bacteria can be detected in the mucus (Caballero et al, 2015;Lourenço et al, 2020) where they are not accessible to bacteriophages present in the lumen. Similarly, several phages have been shown to interact with mucin (Barr et al, 2013;Almeida et al, 2019;Green et al, 2021;Chin et al, 2022) and the presence of phages in the mucus proposed to provide a non-host immunity against 10.3389/fmicb.2023.1266416 Frontiers in Microbiology 08 frontiersin.org invasion or colonization of the gut mucosa by bacteria (Barr et al, 2013), [reviewed extensively in Rothschild-Rodriguez et al, 2022]. This means that bacteria localized in the mucus are, in the absence of mucus associated-bacteriophages targeting them, not visible from bacteriophages that cannot interact with and penetrate in the mucus and are luminal.…”

Advances in bacteriophage-mediated strategies for combating polymicrobial biofilms

“…Some phages and their hosts developed reciprocal predator-prey relationships, e.g., in the intestine, phages may promote the evolution of bacterial resistance to phages in response to infection (Duerkop, 2018). Furthermore, phages may bind to mucin glycoproteins, providing phage-mediated antibacterial protection of animal mucosal surfaces (Barr et al, 2013).…”