Recent studies portend a rising global spread and adaptation of human-or healthcareassociated pathogens. Here, we analyse an international collection of the emerging, multidrug-resistant, opportunistic pathogen Stenotrophomonas maltophilia from 22 countries to infer population structure and clonality at a global level. We show that the S. maltophilia complex is divided into 23 monophyletic lineages, most of which harbour strains of all degrees of human virulence. Lineage Sm6 comprises the highest rate of human-associated strains, linked to key virulence and resistance genes. Transmission analysis identifies potential outbreak events of genetically closely related strains isolated within days or weeks in the same hospitals.

Stenotrophomonas maltophilia is one of the most frequently isolated multidrug resistant nosocomial opportunistic pathogens. It contributes to disease progression in cystic fibrosis patients and is frequently isolated from wounds, infected tissues or catheter surfaces. On these diverse surfaces S. maltophilia lives in single or multi-species biofilms. Since very little is known about common processes in biofilms of different S. maltophilia isolates, we analyzed the biofilm profiles of 300 clinical and environmental isolates from Europe of the recently identified main lineages Sgn3, Sgn4 and Sm2 - Sm18. The analysis of the biofilm architecture of 40 clinical isolates revealed the presence of multicellular structures and high phenotypic variability at a strain-specific level. Further, transcriptome analyses of biofilm cells of seven clinical isolates identified a set of 106 shared strongly expressed genes and 33 strain-specifically expressed genes. Surprisingly, the transcriptome profiles of biofilm versus planktonic cells revealed that just 9.43 ± 1.36 % of all genes were differentially regulated. This implies that just a small set of shared and commonly regulated genes is involved in the biofilm lifestyle. Strikingly, iron uptake appears to be a key factor involved in this metabolic shift. Further, metabolic analyses implied that S. maltophilia employs a mostly fermentative growth mode under biofilm conditions. The transcriptome data of this study together with the phenotypic and metabolic analysis represent so far the largest data set on S. maltophilia biofilm versus planktonic cells. This study will lay the foundation for the identification of strategies for fighting S. maltophilia biofilms in clinical and industrial settings. IMPORTANCE Microorganisms living in a biofilm are much more tolerant to antibiotics and antimicrobial substances than planktonic cells. Thus, the treatment of infections caused by microorganisms living in biofilms is extremely difficult. The nosocomial infections among others caused by S. maltophilia, particularly lung infection among CF patients, increased in prevalence in the last years. The intrinsic multidrug resistance of S. maltophilia and the increased tolerance to antimicrobial agents of its biofilm cells, makes the treatment of S. maltophilia infection difficult. The significance of our research is based in understanding the common mechanisms involved in biofilm formation of different S. maltophilia isolates, understanding the diversity of biofilm architectures among this species and in identifying the differently regulated processes in biofilm versus planktonic cells. These results will lay the foundation for the treatment of S. maltophilia biofilms.

AbstractRecent studies portend a rising global spread and adaptation of human- or healthcare-associated pathogens. Here, we analysed an international collection of the emerging, multidrug-resistant, opportunistic pathogen Stenotrophomonas maltophilia from 22 countries to infer population structure and clonality at a global level. We show that the S. maltophilia complex is divided into 23 monophyletic lineages, most of which harboured strains of all degrees of human virulence. Lineage Sm6 comprised the highest rate of human-associated strains, linked to key virulence and resistance genes. Transmission analysis identified potential outbreak events of genetically closely related strains isolated within days or weeks in the same hospitals.One Sentence SummaryThe S. maltophilia complex comprises genetically diverse, globally distributed lineages with evidence for intra-hospital transmission.

Combating Stenotrophomonas maltophilia biofilms in clinical and industrial settings has proven to be challenging. S. maltophilia is multidrug resistant, and occurrence of resistance to commonly used drugs as well as to antibiotic combinations, such as trimethoprim-sulfamethoxazole, is now frequently reported. It is therefore now necessary to look beyond conventional and already existing antimicrobial drugs when battling S. maltophilia biofilms.

<p><strong>Stenotrophomonas maltophilia</strong><strong> is one of the most frequently isolated multidrug resistant opportunistic pathogens. It contributes to disease progression in cystic fibrosis patients and is found in wounds, other infected tissues and on catheter surfaces. Only little is known on key processes linked to biofilm formation of S. maltophilia on a broader basis. Thus the aim of this study was the identification of key processes involved in biofilm formation of S. maltophilia on a global level. Therefore, we analyzed biofilm profiles of 300 globally collected clinical and environmental isolates of the main and recently identified lineages Sgn3, Sgn4 and Sm2 - Sm18 (Groeschel et al., 2020). These data together with the 3D structural analysis of a subset of clinical 40 clinical isolates revealed an unexpectedly high phenotypic variability on a strain specific level. Further transcriptome analysis of seven clinical isolates using biofilm grown cells identified a set of 106 shared and coexpressed genes and roughly 30-35 strain-specific genes. Based on these findings S. maltophilia employs a mostly fermentative growth modus under the biofilm conditions and uptake of iron, phosphorous and other metals appears to be of high relevance. Surprisingly, the transcriptome profiles of biofilm versus planktonic cells revealed that only 8.6% of all genes were differentially regulated when both conditions were compared.  This implies that only relatively few genes contribute to the change from planktonic to biofilm life style. Thereby iron uptake appears to be a key factor involved in this metabolic shift. The transcriptome data generated in this study together with the phenotypic and metabolic analysis represent so far the largest data set on S. maltophilia biofilm versus planktonic grown cells. This study now lays the foundation for the identification of new strategies in fighting S. maltophilia infections in clinical settings.</strong></p> <p>Ref:  Gröschel et al., 2020 ,The phylogenetic landscape and nosocomial spread of the multidrug-resistant opportunist Stenotrophomonas maltophilia. Nature Commun. 2020 Apr 27;11(1):2044. doi: 10.1038/s41467-020-15123-0.</p>