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Bacterial resistance to temperate phage is influenced by the frequency of lysogenic establishment.

ABSTRACT: Temperate phages can shape bacterial community dynamics and evolution through lytic and lysogenic life cycles. In response, bacteria that resist phage infection can emerge. This study explores phage-based factors that influence bacterial resistance using a model system of temperate P22 phage and Salmonella both inside and outside the mammalian host. Phages that remained functional despite gene deletions had minimal impact on lysogeny and phage resistance except for deletions in the immI region that substantially reduced lysogeny and increased phage resistance to levels comparable to that observed with an obligately lytic P22. This immI deletion does not make the lysogen less competitive but instead increases the frequency of bacterial lysis. Thus, subtle changes in the balance between lysis and lysogeny during the initial stages of infection can significantly influence the extent of phage resistance in the bacterial population. Our work highlights the complex nature of the phage-bacteria-mammalian host triad.

SUBMITTER: Baaziz H

PROVIDER: S-EPMC11016777 | biostudies-literature | 2024 Apr

REPOSITORIES: biostudies-literature

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Bacterial resistance to temperate phage is influenced by the frequency of lysogenic establishment.

Baaziz Hiba H Makhlouf Rita R McClelland Michael M Hsu Bryan B BB

iScience 20240327 4

Temperate phages can shape bacterial community dynamics and evolution through lytic and lysogenic life cycles. In response, bacteria that resist phage infection can emerge. This study explores phage-based factors that influence bacterial resistance using a model system of temperate P22 phage and <i>Salmonella</i> both inside and outside the mammalian host. Phages that remained functional despite gene deletions had minimal impact on lysogeny and phage resistance except for deletions in the <i>imm ...[more]

PMID: 38623331

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Project description:BackgroundTemperate bacteriophages are capable of lysogenic conversion of new bacterial hosts. This phenomenon is often ascribed to "moron" elements that are acquired horizontally and transcribed independently from the rest of the phage genes. Whereas some bacterial species exhibit relatively little prophage-dependent phenotypic changes, other bacterial species such as Stenotrophomonas maltophilia appear to commonly adopt prophage genetic contributions.ResultsThe novel S. maltophilia bacteriophage DLP4 was isolated from soil using the highly antibiotic-resistant S. maltophilia strain D1585. Genome sequence analysis and functionality testing showed that DLP4 is a temperate phage capable of lysogenizing D1585. Two moron genes of interest, folA (BIT20_024) and ybiA (BIT20_065), were identified and investigated for their putative activities using complementation testing and phenotypic and transcriptomic changes between wild-type D1585 and the D1585::DLP4 lysogen. The gp24 / folA gene encodes dihydrofolate reductase (DHFR: FolA), an enzyme responsible for resistance to the antibiotic trimethoprim. I-TASSER analysis of DLP4 FolA predicted structural similarity to Bacillus anthracis DHFR and minimum inhibitory concentration experiments demonstrated that lysogenic conversion of D1585 by DLP4 provided the host cell with an increase in trimethoprim resistance. The gp65 / ybiA gene encodes N-glycosidase YbiA, which in E. coli BW25113 is required for its swarming motility phenotype. Expressing DLP4 ybiA in strain ybiA770(del)::kan restored its swarming motility activity to wildtype levels. Reverse transcription-PCR confirmed the expression of both of these genes during DLP4 lysogeny.ConclusionsS. maltophilia temperate phage DLP4 contributes to the antibiotic resistance exhibited by its lysogenized host strain. Genomic analyses can greatly assist in the identification of phage moron genes potentially involved in lysogenic conversion. Further research is required to fully understand the specific contributions temperate phage moron genes provide with respect to the antibiotic resistance and virulence of S. maltophilia host cells.

Project description:Antibiotic resistance is rapidly spreading via the horizontal transfer of resistance genes in mobile genetic elements. While plasmids are key drivers of this process, few integrative phages encode antibiotic resistance genes. Here, we find that phage-plasmids, elements that are both phages and plasmids, often carry antibiotic resistance genes. We found 60 phage-plasmids with 184 antibiotic resistance genes, providing resistance for broad-spectrum-cephalosporins, carbapenems, aminoglycosides, fluoroquinolones, and colistin. These genes are in a few hot spots, seem to have been cotranslocated with transposable elements, and are often in class I integrons, which had not been previously found in phages. We tried to induce six phage-plasmids with resistance genes (including four with resistance integrons) and succeeded in five cases. Other phage-plasmids and integrative prophages were coinduced in these experiments. As a proof of concept, we focused on a P1-like element encoding an extended spectrum β-lactamase, blaCTX-M-55. After induction, we confirmed that it is capable of infecting and converting four other E. coli strains. Its reinduction led to the further conversion of a sensitive strain, confirming that it is a fully functional phage. This study shows that phage-plasmids carry a large diversity of clinically relevant antibiotic resistance genes that they can transfer across bacteria. As plasmids, these elements seem plastic and capable of acquiring genes from other plasmids. As phages, they may provide novel paths of transfer for resistance genes because they can infect bacteria that are distant in time and space from the original host. As a matter of alarm, they may also mediate transfer to other types of phages. IMPORTANCE The dissemination of antimicrobial resistance is a major threat to global health. Here, we show that a group of temperate bacterial viruses (phages), termed phage-plasmids, commonly encode different and multiple types of resistance genes of high clinical importance, often in integrons. This is unexpected, as phages typically do not carry resistance genes and, hence, do not confer upon their hosts resistance via infection and genome integration. Our experiments with phage-plasmids isolated from clinical settings confirmed that they infect sensitive strains and render them antibiotic resistant. The spread of antibiotic resistance genes by phage-plasmids is worrisome because it dispenses cell-to-cell contact, which is necessary for canonical plasmid transfer (conjugation). Furthermore, their integrons become genetic platforms for the acquisition of novel resistance genes.

Project description:Temperate bacteriophages (phages) are common features of bacterial genomes and can act as self-amplifying biological weapons, killing susceptible competitors and thus increasing the fitness of their bacterial hosts (lysogens). Despite their prevalence, however, the key characteristics of an effective temperate phage weapon remain unclear. Here, we use systematic mathematical analyses coupled with experimental tests to understand what makes an effective temperate phage weapon. We find that effectiveness is controlled by phage life history traits-in particular, the probability of lysis and induction rate-but that the optimal combination of traits varies with the initial frequency of a lysogen within a population. As a consequence, certain phage weapons can be detrimental when their hosts are rare yet beneficial when their hosts are common, while subtle changes in individual life history traits can completely reverse the impact of an individual phage weapon on lysogen fitness. We confirm key predictions of our model experimentally, using temperate phages isolated from the clinically relevant Liverpool epidemic strain of Pseudomonas aeruginosa. Through these experiments, we further demonstrate that nutrient availability can also play a critical role in driving frequency-dependent patterns in phage-mediated competition. Together, these findings highlight the complex and context-dependent nature of temperate phage weapons and the importance of both ecological and evolutionary processes in shaping microbial community dynamics more broadly.ImportanceTemperate bacteriophages-viruses that integrate within bacterial DNA-are incredibly common within bacterial genomes and can act as powerful self-amplifying weapons. Bacterial hosts that carry temperate bacteriophages can thus gain a fitness advantage within a given niche by killing competitors. But what makes an effective phage weapon? Here, we first use a simple mathematical model to explore the factors determining bacteriophage weapon utility. Our models suggest that bacteriophage weapons are nuanced and context-dependent; an individual bacteriophage may be beneficial or costly depending upon tiny changes to how it behaves or the bacterial community it inhabits. We then confirm these mathematical predictions experimentally, using phages isolated from cystic fibrosis patients. But, in doing so, we also find that another factor-nutrient availability-plays a key role in shaping bacteriophage-mediated competition. Together, our results provide new insights into how temperate bacteriophages modulate bacterial communities.

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Bacterial resistance to temperate phage is influenced by the frequency of lysogenic establishment.

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Bacterial resistance to temperate phage is influenced by the frequency of lysogenic establishment.

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