Comparative Genomics of Environmental and Clinical Stenotrophomonas maltophilia Strains with Different Antibiotic Resistance Profiles

Abstract

Stenotrophomonas maltophilia, a ubiquitous Gram-negative γ-proteobacterium, has emerged as an important opportunistic pathogen responsible for nosocomial infections. A major characteristic of clinical isolates is their high intrinsic or acquired antibiotic resistance level. The aim of this study was to decipher the genetic determinism of antibiotic resistance among strains from different origins (i.e., natural environment and clinical origin) showing various antibiotic resistance profiles. To this purpose, we selected three strains isolated from soil collected in France or Burkina Faso that showed contrasting antibiotic resistance profiles. After whole-genome sequencing, the phylogenetic relationships of these 3 strains and 11 strains with available genome sequences were determined. Results showed that a strain's phylogeny did not match their origin or antibiotic resistance profiles. Numerous antibiotic resistance coding genes and efflux pump operons were revealed by the genome analysis, with 57% of the identified genes not previously described. No major variation in the antibiotic resistance gene content was observed between strains irrespective of their origin and antibiotic resistance profiles. Although environmental strains generally carry as many multidrug resistant (MDR) efflux pumps as clinical strains, the absence of resistance-nodulation-division (RND) pumps (i.e., SmeABC) previously described to be specific to S. maltophilia was revealed in two environmental strains (BurA1 and PierC1). Furthermore the genome analysis of the environmental MDR strain BurA1 showed the absence of SmeABC but the presence of another putative MDR RND efflux pump, named EbyCAB on a genomic island probably acquired through horizontal gene transfer.

Keywords: Stenotrophomonas; antibiotic resistance; efflux pump; phylogeny.

Fig. 1.—

Phylogenetic tree from maximum-likelihood analysis of the core-genome alignments of the 14 strains of S. maltophilia and X. campestris pv campestris strain ATCC33913. In total, 1,435 orthologous proteins were concatenated in an alignment of 444,554 amino acids. Bootstraps are indicated at each node. Strains highlighted in green are from environmental origin, in red from clinical origin, and in blue from other origin. Strain names followed by a plain triangle are MDR; those followed by a plain circle are sensitive. Antibiotic resistance profiles of the strains followed by squares are unknown but presence of antibiotic resistance genes was related in the genome references of the strains followed by plain squares.

Fig. 2.—

Summary of the antibiotic resistance genes and operons present in each S. maltophilia strains. Multidrug efflux pumps operons are counted as one even if encoded by multiple genes. No tetracycline and sulfonamide resistance genes were found.

Fig. 3.—

Summary of the known and putative multidrug efflux pumps found in the nine strains of S. maltophilia.

Fig. 4.—

Genetic organization of the ebyCAB genes and adjacent CDS with HGT functions located on a 63-kb genomic island of the chromosome of the strain BurA1. Locus tags are indicated on top of each CDS. CDS colored in green encodes the EbyCAB RND efflux pump specific to the BurA1 strain. CDS colored in yellow and orange are implied in mobile and extrachromosomal element functions, the orange ones belonging to the type IV secretory pathway family. CDS in pink are transcription regulators. INT, integrase; SMC, structural maintenance of chromosome protein.