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Phenotypic Heterogeneity Affects Stenotrophomonas maltophilia K279a Colony Morphotypes and \(\beta\)-Lactamase Expression

Please always quote using this URN: urn:nbn:de:bvb:20-opus-136446
  • Phenotypic heterogeneity at the cellular level in response to various stresses, e.g., antibiotic treatment has been reported for a number of bacteria. In a clonal population, cell-to-cell variation may result in phenotypic heterogeneity that is a mechanism to survive changing environments including antibiotic therapy. Stenotrophomonas rnaltophilia has been frequently isolated from cystic fibrosis patients, can cause numerous infections in other organs and tissues, and is difficult to treat due to antibiotic resistances. S. maltophilia K279aPhenotypic heterogeneity at the cellular level in response to various stresses, e.g., antibiotic treatment has been reported for a number of bacteria. In a clonal population, cell-to-cell variation may result in phenotypic heterogeneity that is a mechanism to survive changing environments including antibiotic therapy. Stenotrophomonas rnaltophilia has been frequently isolated from cystic fibrosis patients, can cause numerous infections in other organs and tissues, and is difficult to treat due to antibiotic resistances. S. maltophilia K279a produces the Li and L2 beta-lactamases in response to beta-lactam treatment. Here we report that the patient isolate S. rnaltophilia K279a diverges into cellular subpopulations with distinct but reversible morphotypes of small and big colonies when challenged with ampicillin. This observation is consistent with the formation of elongated chains of bacteria during exponential growth phase and the occurrence of mainly rod-shaped cells in liquid media. RNA-seq analysis of small versus big colonies revealed differential regulation of at least seven genes among the colony morphotypes. Among those, bleu and bla(L2) were transcriptionally the most strongly upregulated genes. Promoter fusions of b/a(L1) and b/a(L2) genes indicated that expression of both genes is also subject to high levels of phenotypic heterogeneous expression on a single cell level. Additionally, the comE homolog was found to be differentially expressed in homogenously versus heterogeneously bla(L2) expressing cells as identified by RNA(seq) analysis. Overexpression of cornE in S. maltophilia K279a reduced the level of cells that were in a bla(L2)-ON mode to 1% or lower. Taken together, our data provide strong evidence that S. maltophilia K279a populations develop phenotypic heterogeneity in an ampicillin challenged model. This cellular variability is triggered by regulation networks including b/a(L1), b/a(L2), and comE.show moreshow less

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Metadaten
Author: Ebrahim M. Abda, Dagmar Krysciak, Ines Krohn-Molt, Uwe Mamat, Christel Schmeisser, Konrad U. Förstner, Ulrich E. Schaible, Thomas A. Kohi, Stefan Nieman, Wolfgang R. Streit
URN:urn:nbn:de:bvb:20-opus-136446
Document Type:Journal article
Faculties:Medizinische Fakultät / Institut für Molekulare Infektionsbiologie
Language:English
Parent Title (English):Frontiers in Microbiology
Year of Completion:2015
Schriftenreihe:Frontiers in Microbiology 6:1373. doi:10.3389/fmicb.2015.01373
Volume:6
Issue:1373
DOI:https://doi.org/10.3389/fmicb.2015.01373
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Tag:K279a; RNA-seq; Stenotrophomonas maltophilia; antibiotic resistance; beta-lactamases; colony morphotypes; escherichia coli; gram-negative bacteria; membrane vesicles; nosocomial pathogen; persister cells; phenotypic heterogeneity; pseudomas aeruginosa; red fluorescent protein; sinorhizobium fredii NGR234; streptococcus pneumoniae; xanthomonas maltophilia
Release Date:2016/09/02
EU-Project number / Contract (GA) number:278864-2
OpenAIRE:OpenAIRE
Licence (German):License LogoCC BY: Creative-Commons-Lizenz: Namensnennung