Genome Analysis of Anti-Phage Defense Systems and Defense Islands in Stenotrophomonas maltophilia: Preservation and Variability

Abstract

Anti-phage defense systems are widespread in bacteria due to the latter continuous adaptation to infection by bacteriophages (phages). Stenotrophomonas maltophilia has a high degree of intrinsic antibiotic resistance, which makes phage therapy relevant for the treatment of infections caused by this species. Studying the array of anti-phage defense systems that could be found in S. maltophilia helps in better adapting the phages to the systems present in the pathogenic bacteria. Pangenome analysis of the available S. maltophilia strains with complete genomes that were downloaded from GenBank, including five local genomes, indicated a wide set of 72 defense systems and subsystems that varied between the strains. Seven of these systems were present in more than 20% of the studied genomes and the proteins encoded by the systems were variable in most of the cases. A total of 27 defense islands were revealed where defense systems were found; however, more than 60% of the instances of systems were found in four defense islands. Several elements linked to the transfer of these systems were found. No obvious associations between the pattern of distribution of the anti-phage defense systems of S. maltophilia and the phylogenetic features or the isolation site were found.

Keywords: S. maltophilia; anti-phage defense systems; defense islands; phage therapy.

Figure 1

Pangenome analysis of S. maltophilia strains. (A) Matrix of the shared genes between 72 studied strains with taxonomy relatedness; local strains are marked with red circles. (B) Distribution of core and accessory genes in 72 S. maltophilia strains. (C) Distribution of core and accessory genes in five S. maltophilia strains from Novosibirsk.

Figure 2

Putative defense islands of anti-phage defense systems in S. maltophilia. (A) The defense islands mapped to S. maltophilia reference strain NCTC10258. (B) The distribution of anti-phage systems in defense islands.

Figure 3

Defense islands with the highest frequency of occupancy. (A) Defense island #27, occupied by Wadjet I and RecBCD systems. (B) Defense island #4 containing most of RM type II instances and other anti-phage systems. (C) Defense island #16 containing a wide range of various anti-phage defense systems. (D) Defense island #13 containing the most diverse set of anti-phage systems across the studied S. maltophilia strains.

Figure 4

Instances of defense systems found in S. maltophilia strains. Local genomes are marked with red circles.

Figure 5

Classification and conservation of anti-phage defense systems found in S. maltophilia. Blue color marks systems present in one strain, red—in 2–5 strains, green—systems present in more than 5 strains. The genes with bolded borders refer to genes that were not present in all the instances of their systems.

Figure 6

Defense islands occupied by the same anti-phage systems in phylogenetically related strains. (A) Defense islands #19 sharing SoFic system across four relative strains. (B) Defense island #20 containing identical anti-phage systems in two phylogenetically related strains. Reference strain NCTC10258 with empty defense island #20 is shown above.

Figure 7

Examples of defense islands of phylogenetically unrelated strains that are occupied by the same anti-phage defense systems: (A) defense island #18 is occupied by Shedu, (B) defense island #26 is occupied by Dsr I.

Figure 8

Genetic elements linked to the movement of the defense islands between the bacterial strains. Defense islands #5, #15, #17, and #23 are not shown as they do not contain elements associated with carrying defense systems between bacterial genomes.

Figure 9

Anti-phage defense systems (outer rings of each circle), prophages (middle ring) and CAS genes (inner ring) in the S. maltophilia genomes of reference strain NCTC10258 and local strains from Novosibirsk (CEMTC 2142, CEMTC 2355, CEMTC 3659, CEMTC 3664, CEMTC 3670).