Bacteriophages (phages) dramatically shape microbial community composition, redistribute nutrients via host lysis and drive evolution through horizontal gene transfer. Despite their importance, much remains to be learned about phages in the human microbiome. We investigated gut microbiomes of humans from Bangladesh Tanzania, two African baboon social groups Danish pigs; many these contain belonging a clade with genomes >540 kilobases length, largest yet reported microbiome close maximum size...

Bacteriophage predation selects for diverse antiphage systems that frequently cluster on mobilizable defense islands in bacterial genomes. However, molecular insight into the reciprocal dynamics of phage-bacterial adaptations nature is lacking, particularly clinical contexts where there need to inform phage therapy efforts and understand how phages drive pathogen evolution. Using time-shift experiments, we uncovered fluctuations

The Vibrio cholerae lipopolysaccharide O1 antigen is a major target of bacteriophages and the human immune system critical importance for vaccine design. We used an O1-specific lytic bacteriophage as tool to probe capacity V. alter its identified novel mechanism by which this organism can modulate O expression exhibit intra-strain heterogeneity. two phase variable genes required biosynthesis, manA wbeL. resides outside previously recognized biosynthetic locus, encodes phosphomannose...

ABSTRACT Burkholderia is an important bacterial genus with a complex taxonomy that contains species of both ecological and pathogenic importance, including nine closely related collectively termed the cepacia (BCC). In order to more thoroughly investigate virulence this microorganisms, alternative infection models would be useful. To end, we have adapted developed use Galleria mellonella wax moth larvae as host for examining BCC infections. The experimental conditions affecting killing “wax...

Lytic bacteriophages are hypothesized to contribute the seasonality and duration of cholera epidemics in Bangladesh. However, contributing this phenomenon have yet be characterized at a molecular genetic level. In study, we isolated sequenced genomes 15 from stool samples patients spanning 10-year surveillance period Dhaka, Our results indicate that single novel bacteriophage type, designated ICP1 (for International Centre for Diarrhoeal Disease Research, Bangladesh phage 1) is present all...

Vibrio cholerae-specific bacteriophages are common features of the microbial community during cholera infection in humans. Phages impose strong selective pressure that favors expansion phage-resistant strains over their vulnerable counterparts. The mechanisms allowing virulent V. cholerae to defend against ubiquitous threat predatory phages have not been established. Here, we show PLEs (phage-inducible chromosomal island-like elements) widespread genomic islands dedicated phage defense....

The impact of phage predation on bacterial pathogens in the context human disease is not currently appreciated. Here, we show that predatory interactions a with an important environmentally transmitted pathogen, Vibrio cholerae, can modulate evolutionary trajectory this pathogen during natural course infection within individual patients. We analyzed geographically and temporally disparate cholera patient stool samples from Haiti Bangladesh found drive genomic diversity intra-patient V....

The classical and El Tor biotypes of Vibrio cholerae serogroup O1, the etiological agent cholera, are responsible for sixth seventh (current) pandemics, respectively. A genomic island (GI), GI-24, previously identified in a biotype strain V. cholerae, is predicted to encode clustered regularly interspaced short palindromic repeat (CRISPR)-associated proteins (Cas proteins); however, experimental evidence support CRISPR activity has not been documented. Here, we show that CRISPR-Cas...

Bacteriophages or phages-viruses of bacteria-are abundant and considered to be highly diverse. Interestingly, a particular group lytic Vibrio cholerae-specific phages (vibriophages) the International Centre for Diarrheal Disease Research, Bangladesh cholera phage 1 (ICP1) lineage show high levels genome conservation over large spans time geography, despite constant coevolutionary arms race with their host. From collection 67 sequenced ICP1 isolates, mostly from clinical samples, we find...

Abstract In 2022, one of its worst cholera outbreaks began in Bangladesh and the icddr,b Dhaka hospital treated more than 1300 patients ca. 42,000 diarrheal cases from March-1 to April-10, 2022 1 . Here, we present genomic attributes V. cholerae O1 responsible for outbreak 960 7th pandemic El Tor (7PET) strains 88 countries. Results show isolated during cluster with 7PET wave-3 global clade strains, but comprise subclade BD-1.2, which most recent common ancestor appears be that endemic...

Abstract Bacteria harness diverse defense systems that protect against phage predation 1 , many of which are encoded on horizontally transmitted mobile genetic elements (MGEs) 2 . In turn, phages evolve counter-defenses 3 driving a dynamic arms race remains underexplored in human disease contexts. For the diarrheal pathogen Vibrio cholerae higher burden its lytic phage, ICP1, patient stool correlates with reduced severity 4 However, direct molecular evidence phage-driven selection epidemic...

Vibrio cholerae, the causative agent of diarrheal disease cholera, is antagonized by lytic phage ICP1 in aquatic environment and human hosts. Mobile genetic elements called PLEs (phage-inducible chromosomal island-like elements) protect V. cholerae from infection initiate their anti-phage response excising chromosome. Here, we show that PLE 1 encodes a large serine recombinase, Int, exploits an ICP1-specific protein as recombination directionality factor (RDF) to excise infection. We this...

Bacteria, bacteriophages that prey upon them, and mobile genetic elements (MGEs) compete in dynamic environments, evolving strategies to sense the milieu. The first discovered environmental sensing by phages, lysis inhibition, has only been characterized studied limited context of T-even coliphages. Here, we discover inhibition etiological agent diarrheal disease cholera, Vibrio cholerae, infected ICP1, a phage ubiquitous clinical samples. This work identifies ICP1-encoded holin, teaA,...

Mobile genetic elements, elements that can move horizontally between genomes, have profound effects on their host's fitness. The phage-inducible chromosomal island-like element (PLE) is a mobile integrates into the chromosome of Vibrio cholerae and parasitizes bacteriophage ICP1 to cells. This parasitism by PLE such it abolishes production progeny provides defensive boon host cell population. In response severe imposed PLE, has acquired an adaptive CRISPR-Cas system targets genome during...

PLEs (phage-inducible chromosomal island-like elements) are phage parasites integrated into the chromosome of epidemic Vibrio cholerae. In response to infection by its viral host ICP1, PLE excises, replicates and hijacks ICP1 structural components for transduction. Through an unknown mechanism, prevents from transitioning rolling circle replication (RCR), a prerequisite efficient packaging genome. Here, we characterize PLE-encoded nuclease, NixI, that blocks development likely nicking ICP1's...

Vibrio cholerae is a significant threat to global public health in part due its propensity for large-scale evolutionary sweeps where lineages emerge and are replaced. These may originate from the Bay of Bengal, bacteriophage predation evolution antiphage counterdefenses recurring theme. The ICP1 key predator epidemic V. notable acquiring CRISPR-Cas system combat PLE, defensive subviral parasite encoded by host. Here, we describe discovery four previously unknown PLE variants through...

Phage satellites commonly remodel capsids they hijack from the phages parasitize, but only a few mechanisms regulating change in capsid size have been reported. Here, we investigated how satellite Vibrio cholerae , phage-inducible chromosomal island-like element (PLE), remodels it has predicted to steal phage ICP1 (Netter et al., 2021). We identified that PLE-encoded protein, TcaP, is both necessary and sufficient form small during infection. Interestingly, found PLE dependent on for...

The Burkholderia cepacia complex (BCC) is a group of bacterial pathogens that are highly antibiotic resistant and associated with debilitating respiratory infections. Although bacteriophages the BCC have been isolated characterized, no studies yet examined phage therapy against in vivo. In caterpillar infection model, we show an alternative treatment possibility effective under specific conditions.

Significance Bacterial pathogens evolve rapidly in the face of clinical interventions and therapeutics; one mechanism that can promote this evolution is their ability to acquire novel DNA sequences, known as horizontal gene transfer (HGT). Here, we studied HGT isolates Vibrio cholerae , causative agent cholera, found a horizontally transferred element inhibits another HGT—natural transformation. The natural transformation globally distributed among V. isolates. We show, however, there has...

CRISPR-Cas systems function as adaptive immune by acquiring nucleotide sequences called spacers that mediate sequence-specific defence against competitors. Uniquely, the phage ICP1 encodes a Type I-F system is deployed to target and overcome PLE, mobile genetic element with anti-phage activity in Vibrio cholerae. Here, we exploit arms race between PLE examine spacer acquisition interference under laboratory conditions reconcile findings from wild populations. Natural isolates encode multiple...

Abstract Background One of the most significant public health concerns in today’s world is persistent upsurge infections caused by multidrug resistant bacteria. As a result, clinicians are being forced to intervene with either less effective backup drugs or ones substantial side-effects. Colistin last resort antimicrobial agent for treatment multi-drug gram-negative Methods Escherichia coli (n = 65) isolated from street food 20), hand rinse 15), surface water 10), and healthy human stool 20)...

Phage-inducible chromosomal island-like elements (PLEs) are bacteriophage satellites found in Vibrio cholerae. PLEs parasitize the lytic phage ICP1, excising from bacterial chromosome, replicating, and mobilizing to new host cells following cell lysis. protect their populations by completely restricting production of ICP1 progeny. Previously, it was that replication reduced during PLE(+) infection. Despite robust PLE genome, relatively few transducing units produced. We investigated if DNA...

Abstract Bacteria persist under constant threat of predation by bacterial viruses (phages). Bacteria-phage conflicts result in evolutionary arms races often driven mobile genetic elements (MGEs). One such MGE, a phage satellite Vibrio cholerae called PLE, provides specific and robust defense against pervasive lytic phage, ICP1. The interplay between PLE ICP1 has revealed strategies for molecular parasitism allowing to hijack processes order mobilize. Here, we describe the mechanism...