Govindan, A. R. | bioRxiv Science

bioRxiv2019

The population and evolutionary dynamics of bacteriophage: Why be temperate revisited

Bacteriophages are deemed either lytic (virulent) or temperate, respectively depending on whether their genomes are transmitted solely horizontally, or both horizontally and vertically. To elucidate the ecological and evolutionary conditions under which natural selection will favor the evolution and maintenance of lytic or temperate modes of phage replication and transmission, we use a comprehensive mathematical model of the dynamics of temperate and virulent phage in populations of bacteria sensitive and resistant to these viruses. For our numerical analysis of the properties of this model, we use parameters estimated with the temperate bacteriophage Lambda, {lambda}, its clear and virulent mutants, and E. coli sensitive and resistant - refractory to these phages. Using batch and serial transfer population dynamic and reconstruction experiments, we test the hypotheses generated from this theoretical analysis. Based on the results of this jointly theoretical and experimental study, we postulate the conditions under which natural selection will favor the evolution and maintenance of lytic and temperate modes of phage replication and transmission. A compelling and novel prediction this in silico, in vitro, and in plastico study makes is lysogenic bacteria from natural populations will be resistant-refractory to the phage for which they are lysogenic as well as lytic phage sharing the same receptors as these temperate viruses.

evolutionary biology↗

bioRxiv2018

Antibiotic killing of diversely generated populations of non-replicating bacteria

Non-replicating bacteria are known to be (or at least commonly thought to be) refractory to antibiotics to which they are genetically susceptible. Here, we explore the sensitivity to antibiotic-mediated killing of three classes of non-replicating populations of planktonic bacteria (1) stationary phase, when the concentration of resources and/or nutrients are too low to allow for population growth; (2) persisters, minority subpopulations of susceptible bacteria surviving exposure to bactericidal antibiotics; (3) antibiotic-static cells, bacteria exposed to antibiotics that prevent their replication but kill them slowly if at all, the so-called bacteriostatic drugs. Using experimental populations of Staphylococcus aureus Newman and Escherichia coli K12 and respectively 14 and 11 different antibiotics, we estimate the rates at which these drugs kill these different types of non-replicating bacteria. Contrary to the common belief that bacteria that are non-replicating are refractory to antibiotic-mediated killing, all three types of non-replicating populations of these Gram-positive and Gram-negative bacteria are consistently killed by aminoglycosides and the peptide antibiotics, daptomycin and colistin, respectively. This result indicates that non-replicating cells, irrespectively of why they do not replicate, have an almost identical response to the cidal activity of antibiotics. We discuss the implications of these results to our understanding of the mechanisms of action of antibiotics and the possibility of adding a short-course of aminoglycosides or peptide antibiotics to conventional therapy of bacterial infections.

microbiology↗