Competition between lysogenic and sensitive bacteria is determined by the fitness costs of the different emerging phage-resistance strategies

Abstract

Many bacterial genomes carry prophages whose induction can eliminate competitors. In response, bacteria may become resistant by modifying surface receptors, by lysogenization, or by other poorly known processes. All these mechanisms affect bacterial fitness and population dynamics. To understand the evolution of phage resistance, we co-cultivated a phage-sensitive strain (BJ1) and a poly-lysogenic Klebsiella pneumoniae strain (ST14) under different phage pressures. The population yield remained stable after 30 days. Surprisingly, the initially sensitive strain remained in all populations and its frequency was highest when phage pressure was strongest. Resistance to phages in these populations emerged initially through mutations preventing capsule biosynthesis. Protection through lysogeny was rarely observed because the lysogens have increased death rates due to prophage induction. Unexpectedly, the adaptation process changed at longer time scales the frequency of capsulated cells in BJ1 populations increased again, because the production of capsule was fine-tuned, reducing the ability of phage to absorb. Contrary to the lysogens, these capsulated resistant clones are pan-resistant to a large panel of phages. Intriguingly, some clones exhibited transient non-genetic resistance to phages, suggesting an important role of phenotypic resistance in coevolving populations. Our results show that interactions between lysogens and sensitive strains are shaped by antagonistic co-evolution between phages and bacteria. These processes may involve key physiological traits, such as the capsule, and depend on the time frame of the evolutionary process. At short time scales, simple and costly inactivating mutations are adaptive, but in the long-term, changes drawing more favorable trade-offs between resistance to phages and cell fitness become prevalent.

Defence systems and horizontal gene transfer in bacteria

“…Thus, the effects of defence systems on HGT appear to be strongly lineage‐specific and depend on additional factors. Integrated phages and plasmids can impose various metabolic and other fitness costs on their hosts contingent upon ecological and genetic contexts (Alonso‐Del Valle et al, 2021; Rendueles et al, 2023). Hence, there is likely a differential selection pressure on the same types of defence systems in different species to hinder the spread of MGEs, depending on the associated costs of the latter.…”

Defense systems and horizontal gene transfer in bacteria

“…Thus, the effects of defense systems on HGT appear to be strongly lineage-specific and depend on additional factors. Integrated phages and plasmids can impose various metabolic and other fitness costs on their hosts contingent upon ecological and genetic contexts ( Alonso-Del Valle et al, 2021 ; Rendueles et al, 2023 ). Hence, there is likely a differential selection pressure on same types of defense systems in different species to hinder the spread of MGEs, depending on the associated costs of the latter.…”

Anti-CRISPR proteins trigger a burst of CRISPR-Cas9 expression that enhances phage defense

“…Lysogeny can be costly for bacteria due to the disruption of genes surrounding the integration site, the increased genomic size, and the threat of lysis during DNA damage. 41 , 42 However, lysogeny is also a mode for the horizontal transfer of beneficial genes, like those involved in antibiotic-resistance, phage defense, and pathogenicity. 43 , 44 CRISPR-Cas induction may therefore provide short-term benefits by reducing lysis and reducing genome expansion while limiting the potential for adoption of new genetic material.…”