Pseudomonas aeruginosa is an opportunistic pathogen that can cause infections in humans, especially in hospital patients with compromised host defence mechanisms, including patients with cystic fibrosis. Filamentous bacteriophages represent a group of single-stranded DNA viruses infecting different bacteria, including P. aeruginosa and other human and animal pathogens; many of them can replicate when integrated into the bacterial chromosome. Filamentous bacteriophages can contribute to the virulence of P. aeruginosa and influence the course of the disease. There are just a few isolated and officially classified filamentous bacteriophages infecting P. aeruginosa, but genomic studies indicated the frequent occurrence of integrated prophages in many P. aeruginosa genomes. An analysis of sequenced genomes of P. aeruginosa isolated from upper respiratory tract (throat and nasal swabs) and sputum specimens collected from Russian patients with cystic fibrosis indicated a higher diversity of filamentous bacteriophages than first thought. A detailed analysis of predicted bacterial proteins revealed prophage regions representing the filamentous phages known to be quite distantly related to known phages. Genomic comparisons and phylogenetic studies enabled the proposal of several new taxonomic groups of filamentous bacteriophages.

Pseudomonas aeruginosa is characterized by a high adaptive potential, developing resistance in response to antimicrobial pressure. We employed a spatiotemporal evolution model to disclose the pathways of adaptation to colistin, a last-resort polymyxin antimicrobial, among three unrelated P. aeruginosa lineages. The P. aeruginosa ATCC-27833 reference strain (Pa_ATCC), an environmental P. aeruginosa isolate (Pa_Environment), and a clinical isolate with multiple drug resistance (Pa_MDR) were grown over an increasing 5-step colistin concentration gradient from 0 to 400 mg/L. Pa_Environment demonstrated the highest growth pace, achieving the 400 mg/L band in 15 days, whereas it took 37 and 60 days for Pa_MDR and Pa_ATCC, respectively. To identify the genome changes that occurred during adaptation to colistin, the isolates selected during the growth of the bacteria (n = 185) were subjected to whole genome sequencing. In total, 17 mutation variants in eight lipopolysaccharide-synthesis-associated genes were detected. phoQ and lpxL/PA0011 were affected in all three lineages, whereas changes in pmrB were found in Pa_Environment and Pa_MDR but not in Pa_ATCC. In addition, mutations were detected in 34 general metabolism genes, and each lineage developed mutations in a unique set of such genes. Thus, the three examined distinct P. aeruginosa strains demonstrated different capabilities and genetic pathways of colistin adaptation.

Bacteria survival in the conditions of antimicrobial therapy is the global problem of health care. This review highlights the complexity and diversity of mechanisms used by bacteria to neutralize antibiotics. To analyze the problem, the search was made using PubMed database, Russian scientific electronic library eLIBRARY, search system of World Health Organization and European Society of Clinical Microbiology and Infectious Diseases (ESCMID). Based on the analysis of survival strategies in the conditions of antibiotics action we propose new classification of resistant bacteria. Classification criteria include the ability to divide under antibiotics action, the survival strategies application as a species trait, the presence of specialized genes determining the transition to the state with reduced/stopped metabolism. Two main groups are resistant bacteria and bacteria with reduced/stopped metabolism, which survive but do not divide in the presence of antibiotic. The first group includes two subgroups: bacteria with intrinsic and adaptive resistance. The second group includes (1) bacteria with specialized genes responsible for cell transformation to the state with reduced/stopped metabolism, (2) bacteria transforming to the state with reduced/stopped metabolism without involvement of special genes, and (3) cell forms with special morphology - spores, cysts and cyst-like cells. We described the usefulness of proposed classification including improved understanding of the correlation between bacteria survival in the presence of antibiotics and molecular mechanism of cell metabolism inhibition, presence or absence of targets for using molecular-genetic methods of bacteria resistant variant determination, the possibility for development of rational antimicrobial therapy methods.