Mutation in the C-Di-AMP Cyclase dacA Affects Fitness and Resistance of Methicillin Resistant Staphylococcus aureus

• DOI: 10.1371/journal.pone.0073512
• Publication Date: 2013-08-27T21:38:03Z
• Authors: Vanina Dengler; Nadine McCallum; Patrick Kiefer; Philipp Christen; Andrea Patrignani; Julia A. Vorholt; Brigitte Berger-B...; Maria M. Senn
• Keywords: Methicillin-Resistant Staphylococcus aureus; 0301 basic medicine; 1000 Multidisciplinary; 10179 Institute of Medical Microbiology; Science; Q; R; 610 Medicine & health; 1100 General Agricultural and Biological Sciences; 3. Good health; 03 medical and health sciences; Bacterial Proteins; 1300 General Biochemistry, Genetics and Molecular Biology; Drug Resistance, Bacterial; Mutation; 570 Life sciences; biology; Medicine; Phosphorus-Oxygen Lyases; Research Article

Faster growing and more virulent strains of methicillin resistant Staphylococcus aureus (MRSA) are increasingly displacing highly MRSA. Elevated fitness in these MRSA is often accompanied by decreased heterogeneous levels resistance; however, the mechanisms for this phenomenon not yet fully understood. Whole genome sequencing was used to investigate genetic basis apparent correlation, an isogenic strain pair that differed resistance fitness, with respect growth rate. Sequencing revealed only one single nucleotide polymorphism (SNP) diadenylate cyclase gene dacA faster but less strain. Diadenylate cyclases were recently discovered synthesize new second messenger cyclic diadenosine monophosphate (c-di-AMP). Introduction mutation into slower reduced increased its rate, suggesting a direct connection between phenotypic differences strains. Quantification cellular c-di-AMP resulting autolysis, salt tolerance reduction basal expression cell wall stress stimulon. These results indicate affects envelope-related signalling S. aureus. The influence on rate altering could be mechanism which can increase their reducing levels.