The global phylogenetic landscape and nosocomial spread of the multidrug-resistant opportunistStenotrophomonas maltophilia

Abstract

<jats:title>Abstract</jats:title><jats:p>Recent 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 <jats:italic>Stenotrophomonas maltophilia</jats:italic> from 22 countries to infer population structure and clonality at a global level. We show that the <jats:italic>S. maltophilia</jats:italic> 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.</jats:p><jats:sec><jats:title>One Sentence Summary</jats:title><jats:p>The <jats:italic>S. maltophilia</jats:italic> complex comprises genetically diverse, globally distributed lineages with evidence for intra-hospital transmission.</jats:p></jats:sec>

Synthesis of Natural Rubrolides B, I, K, L, M, O and Analogues

“…Rubrolides B 1 , I 2 , K 3 , L 4 , M 5 , O 6 and the synthesized analogues were tested for their antibiofilm and antiviral properties. Investigating the reduction of virus replication of two different influenza A virus subtypes [28,29] and biofilm formation of Stenotrophomonas maltophilia [30–32] . For the virus inhibition, MDCK (Madin‐Darby canine kidney) cells were infected with p H1N1 or H3N2 influenza A viruses and cotreated with Ribavirin or the synthesized rubrolides (for all data see Supporting Information).…”

“…Furthermore, all synthesized natural rubrolides B 1 , I 2 , K 3 , L 4 , M 5 , O 6 and their synthetic analogues 19 – 25 and 27 had a significant antibiofilm activity against Stenotrophomonas maltophilia K279a. The treatment of S. maltophilia biofilms is very important since it is an emerging and highly multidrug resistant pathogen, which is often co‐isolated from wounds, catheters and other medical devices together with P. aeruginosa , S. aureus and other relevant pathogens [32,33] . The strongest effect was achieved by rubrolide B 1 , which reduced the biofilm formation by 84.6±15.0 % at 100 μg/mL.…”

“…The strongest effect was achieved by rubrolide B 1 , which reduced the biofilm formation by 84.6±15.0 % at 100 μg/mL. The biofilm was analyzed as previously described [32–34] …”

“…Investigating the reduction of virus replication of two different influenza A virus subtypes [28,29] and biofilm formation of Stenotrophomonas maltophilia. [30][31][32] For the virus inhibition, MDCK (Madin-Darby canine kidney) cells were infected with pH1N1 or H3N2 influenza A viruses and cotreated with Ribavirin or the synthesized rubrolides (for all data see Supporting Information). The viral titer of infected and PBS (phosphate buffer saline) (Ctrl 1) or 0.1 % DMSO (Ctrl 2) treated cells served as negative control.…”

“…The treatment of S. maltophilia biofilms is very important since it is an emerging and highly multidrug resistant pathogen, which is often co-isolated from wounds, catheters and other medical devices together with P. aeruginosa, S. aureus and other relevant pathogens. [32,33] The strongest effect was achieved by rubrolide B 1, which reduced the biofilm formation by 84.6 � 15.0 % at 100 μg/mL. The biofilm was analyzed as previously described.…”