Moscoso, MiriamDomenech Lucas, MiriamGarcía, Ernesto2024-02-012024-02-012010Moscoso, Miriam, et al. «Vancomycin Tolerance in Clinical and Laboratory Streptococcus Pneumoniae Isolates Depends on Reduced Enzyme Activity of the Major LytA Autolysin or Cooperation between CiaH Histidine Kinase and Capsular Polysaccharide». Molecular Microbiology, vol. 77, n.o 4, agosto de 2010, pp. 1052-64. https://doi.org/10.1111/j.1365-2958.2010.07271.x.0950-382X10.1111/j.1365-2958.2010.07271.xhttps://hdl.handle.net/20.500.14352/97516Partial support for these investigations was provided by Grant SAF2009-10824 from Dirección General de Investigación Científica yTécnica. Centro de Investigación Biomédica en Red de Enfermedades Respiratorias(CIBERES) is an initiative of the ISCIII Additional funding was provided by the COMBACT program(S-BIO-0260/2006) of the Comunidad de Madrid. M.D.was supported by an FPI fellowship from the Ministerio de Ciencia e Innovación.Vancomycin is frequently added to standard therapy for pneumococcal meningitis. Although vancomycin-resistant Streptococcus pneumoniae strains have not been isolated, reports on the emergence of vancomycin-tolerant pneumococci are a cause of concern. To date, the molecular basis of vancomycin tolerance in S. pneumoniae is essentially unknown. We examined two vancomycin-tolerant clinical isolates, i.e. a purported autolysin negative (LytA-), serotype 23F isolate (strain S3) and the serotype 14 strain ‘Tupelo’, which is considered a paradigm of vancomycin tolerance. S3 was characterized here as carrying a frameshift mutation in the lytA gene encoding the main pneumococcal autolysin. The vancomycin tolerance of strain S3 was abolished by transformation to the autolysin-proficient phenotype. The original Tupelo strain was discovered to be a mixture: a strain showing a vancomycin-tolerant phenotype (Tupelo_VT) and a vancomycin-nontolerant strain (Tupelo_VNT). The two strains differed only in terms of a single mutation in the ciaH gene present in the VT strain. Most interestingly, although the vancomycin tolerance of Tupelo_VT could be overcome by increasing the LytA dosage upon transformation by a multicopy plasmid or by externally adding the autolysin, we show that vancomycin tolerance in S. pneumoniae requires the simultaneous presence of a mutated CiaH histidine kinase and capsular polysaccharide.engjournal article1365-2958https://doi.org/10.1111/j.1365-2958.2010.07271.xrestricted access579.25GenéticaMicrobiología (Biología)2409 Genética2414 Microbiología