Biology subjects

Gomez, J. B.

Publications and source records attributed to Gomez, J. B..

3 recordsLinked to original sources

bioRxiv2025

Phages use contingency loci as a bet-hedging strategy

Bacteriophages are estimated to outnumber bacteria by [~]10-fold1,2. Here, we show that phage genomes contain contingency loci (CL), hypermutable DNA regions that promote reversible frameshift mutations through DNA polymerase slippage3-6. CL have been described in bacteria, archaea, and eukaryotes but have not previously been reported in phages. We demonstrate that CL in coliphage T2 and T4 generates genomic and phenotypic diversity in resulting progeny to evade host defense, a process known as bet-hedging. Whole genome sequencing of T2 and T4 show similar levels of CL-driven sequence variation in dozens of other putative CL. Additional sequencing of T6, T7, Sec{varphi}27, ICP1 and ICP2, alongside bioinformatics of the BASEL phage collection reveals that putative CL are widespread in phages and are encoded in every functional class of genes. Collectively, our study describes a new paradigm for understanding phage replication in which CL drive genetic diversification and population heterogeneity to rapidly evolve.

microbiology↗

bioRxiv2024

A Vibrio cholerae Type IV restriction system targets glucosylated 5-hydroxyl methyl cytosine to protect against phage infection

A major challenge faced by Vibrio cholerae is constant predation by bacteriophage (phage) in aquatic reservoirs and during infection of human hosts. To overcome phage predation, V. cholerae has evolved a myriad of phage defense systems. Although several novel defense systems have been discovered, we hypothesized more were encoded in V. cholerae given the relative paucity of phage that have been isolated which infect this species. Using a V. cholerae genomic library, we identified a Type IV restriction system consisting of two genes within a 16kB region of the Vibrio pathogenicity island-2 that we name TgvA and TgvB (Type I-embedded gmrSD-like system of VPI-2). We show that both TgvA and TgvB are required for defense against T2, T4, and T6 by targeting glucosylated 5-hydroxymethylcytosine (5hmC). T2 or T4 phages that lose the glucose modification are resistant to TgvAB defense but exhibit a significant evolutionary tradeoff becoming susceptible to other Type IV restriction systems that target unglucosylated 5hmC. We show that additional phage defense genes are encoded in VPI-2 that protect against other phage like T3, sec{Phi}18, sec{Phi}27 and {lambda}. Our study uncovers a novel Type IV restriction system in V. cholerae, increasing our understanding of the evolution and ecology of V. cholerae while highlighting the evolutionary interplay between restriction systems and phage genome modification. Abstract ImportanceBacteria are constantly being predated by bacteriophage (phage). To counteract this predation, bacteria have evolved a myriad of defense systems. Some of these systems specifically digest infecting phage by recognizing unique base modifications present on the phage DNA. Here, we discover a Type IV restriction system encoded in V. cholerae that we name TgvAB and demonstrate it recognizes and restricts phage that have 5-hydroxymethylcytosine glucosylated DNA. Moreover, the evolution of resistance to TgvAB render phage susceptible to other Type IV restriction systems, demonstrating a significant evolutionary tradeoff. These results enhance our understanding of the evolution of V. cholerae and more broadly how bacteria evade phage predation.

microbiology↗

bioRxiv2019

Historical contingency in the evolution of antibiotic resistance after decades of relaxed selection

Populations often encounter changed environments that remove selection for the maintenance of particular phenotypic traits. The resulting genetic decay of those traits under relaxed selection reduces an organisms fitness in its prior environment. However, whether and how such decay alters the subsequent evolvability of a population upon restoration of selection for a previously diminished trait is not well understood. We addressed this question using Escherichia coli strains from the long-term evolution experiment (LTEE) that independently evolved for multiple decades in the absence of antibiotics. We first confirmed that these derived strains are typically more sensitive to various antibiotics than their common ancestor. We then subjected the ancestral and derived strains to various concentrations of these drugs to examine their potential to evolve increased resistance. We found that evolvability was idiosyncratic with respect to initial genotype; that is, the derived strains did not generally compensate for their greater susceptibility by \"catching up\" to the resistance level of the ancestor. Instead, the capacity to evolve increased resistance was constrained in some backgrounds, implying that evolvability depended upon prior mutations in a historically contingent fashion. We further subjected a time-series of clones from one LTEE population to tetracycline and determined that an evolutionary constraint arose early in that population, corroborating the role of contingency. In summary, relaxed selection not only can drive populations to increased antibiotic susceptibility, but it can also affect the subsequent evolvability of antibiotic resistance in an unpredictable manner. This conclusion has potential implications for public health, and it underscores the need to consider the genetic context of pathogens when designing drug-treatment strategies.

evolutionary biology↗