Substances based on natural fungal compounds inhibit the biofilm of various Stenotrophomonas maltophilia isolates

<p><em>Stenotrophomonas maltophilia</em> is a multidrug resistant human nosocomial opportunistic pathogen. It contributes to disease progression in cystic fibrosis patients and is found in wounds, other infected tissues and on catheter surfaces. <em>S. maltophilia</em> is globally distributed and forms 23 distinct phylogenetic clusters (1, 2). Due to its multidrug resistance, it is extremely difficult to heal <em>S. maltophilia</em> caused infections. Colistin is a last-resort antibiotic against multidrug resistant pathogens. However, this study reveals that the minimal inhibitory concentration (MIC) of colistin varies strongly between 22 tested clinical isolates by ranging from 6.25 - >100 µg/ml. The minimal biofilm inhibitory concentration (MBIC) was detected to be much higher. On 41% of the isolates, colistin proved to be very effective on planktonic cells (MIC-value ≤6.25 µg/ml), but less effective on biofilm cells represented by only 18% of the isolates (MBIC-value <100 µg/ml). Thus, we screened for substances, which prevented specifically the biofilm formation or were involved in the removal of established biofilms. We identified several natural fungal compounds and synthetically produced analogues that affect the biofilm of <em>S. maltophilia</em>. In microtiter plate assays, the three substances HH-R6, HH-R8 and HH-R9, which belong to the rubrolides, had with 63 - 83 % the strongest biofilm reduction effect on the biofilm of <em>S. maltophilia</em> K279a. However, microscopy of the biofilms still revealed some living adhered cells although the biofilm structure was strongly impaired. Furthermore, the antibiofilm effect and the impact on the biofilm structure varied strongly among different clinical <em>S. maltophilia</em> isolates. Ongoing transcriptome analyses are expected to shed light on the biofilm inhibiting mechanism of these substances and to get further evidences how they can be used in a clinical setting in the future.</p> <p> </p> <p>1   Steinmann J., Mamat U., Abda E.M., <em>et al</em>. Analysis of Phylogenetic Variation of <em>Stenotrophomonas maltophilia</em> Reveals Human-Specific Branches. Front Microbiol. 2018, 9:806 (2018). doi:10.3389/fmicb.2018.00806</p> <p>2   Gröschel, M.I., Meehan, C.J., Barilar, I. <em>et al</em>. The phylogenetic landscape and nosocomial spread of the multidrug-resistant opportunist <em>Stenotrophomonas maltophilia</em>. Nat Commun 11, 2044 (2020). https://doi.org/10.1038/s41467-020-15123-0</p>