TITLE

The Evolutionary History of Amino Acid Variations Mediating Increased Resistance of S. aureus Identifies Reversion Mutations in Metabolic Regulators

AUTHOR(S)
Champion, Mia D.; Gray, Vanessa; Eberhard, Carl; Kumar, Sudhir
PUB. DATE
February 2013
SOURCE
PLoS ONE;Feb2013, Vol. 8 Issue 2, p1
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
The evolution of resistance in Staphylococcus aureus occurs rapidly, and in response to all known antimicrobial treatments. Numerous studies of model species describe compensatory roles of mutations in mediating competitive fitness, and there is growing evidence that these mutation types also drive adaptation of S. aureus strains. However, few studies have tracked amino acid changes during the complete evolutionary trajectory of antibiotic adaptation or been able to predict their functional relevance. Here, we have assessed the efficacy of computational methods to predict biological resistance of a collection of clinically known Resistance Associated Mutations (RAMs). We have found that >90% of known RAMs are incorrectly predicted to be functionally neutral by at least one of the prediction methods used. By tracing the evolutionary histories of all of the false negative RAMs, we have discovered that a significant number are reversion mutations to ancestral alleles also carried in the MSSA476 methicillin-sensitive isolate. These genetic reversions are most prevalent in strains following daptomycin treatment and show a tendency to accumulate in biological pathway reactions that are distinct from those accumulating non-reversion mutations. Our studies therefore show that in addition to non-reversion mutations, reversion mutations arise in isolates exposed to new antibiotic treatments. It is possible that acquisition of reversion mutations in the genome may prevent substantial fitness costs during the progression of resistance. Our findings pose an interesting question to be addressed by further clinical studies regarding whether or not these reversion mutations lead to a renewed vulnerability of a vancomycin or daptomycin resistant strain to antibiotics administered at an earlier stage of infection.
ACCESSION #
87624635

 

Related Articles

  • Mother's Day. Monaco, John E. // Pediatrics for Parents;2007, Vol. 23 Issue 6, p6 

    The article discusses the author's experience at the children's hospital. He saw Kathleen, a two year old girl who had been infected with Methicillin-resistant Staphylococcus Aureus (MRSA), which is primarily responsible for skin and soft tissue infection. He showed his daughter how to examine...

  • Could new antibiotic have MRSA in its sights?  // Pharmaceutical Technology Europe;Jul2006, Vol. 18 Issue 7, p10 

    The article reports that researchers have developed platensimycin which could be used against methicillin-resistant Staphylococcus aureus. The drug is produced by Streptomyces platensis and is the most potent inhibitor of the FabF enzyme. FabF is utilized in fatty acid formation if bacterial...

  • Benchmarking antibiotic use in Finnish acute care hospitals using patient case-mix adjustment. Kanerva, Mari; Ollgren, Jukka; Lyytikäinen, Outi // Journal of Antimicrobial Chemotherapy (JAC);Nov2011, Vol. 66 Issue 11, p2651 

    Objectives It is difficult to draw conclusions about the prudence of antibiotic use in different hospitals by directly comparing usage figures. We present a patient case-mix adjustment model of antibiotic use to rank hospitals while taking patient characteristics into account. Patients and...

  • Antimicrobial resistance of Staphylococcus aureus strains from patients with urinary tract infections in Yenagoa, Nigeria. Onanuga, Adebola; Awhowho, Godwin Oghenekparobo // Journal of Pharmacy & Bioallied Sciences;Jul-Sep2012, Vol. 4 Issue 3, p226 

    Context: Antimicrobial resistance in Staphylococcus aureus infections is a global public health problem resulting in very limited treatment options. This study determined the antimicrobial resistance pattern of S. aureus strains from urinary tract infections (UTIs) to commonly used antimicrobial...

  • Cochrane review - MRSA eradication. Tanner, Judith // British Journal of Perioperative Nursing;Aug2004, Vol. 14 Issue 8, p333 

    Discusses a research about the effects of topical and systemic antimicrobial agants on nasal and extra-nasal methicillin-resistant staphylococcus aureus (MRSA). Occurrence of adverse events and development of antimicrobial resistance with the use of the therapy.

  • Microbial Resistance: An Overview for Oral Health Providers. Depaola, Louis G.; Fried, Jacquelyn I. // Access;Mar2008, Vol. 22 Issue 3, p42 

    The article focuses on the growing concern over antimicrobial resistance, which refers to the ability of bacteria and other microorganisms to resist effects of antibiotics and antimicrobial agents. Several factors leading to the development of antimicrobial resistance are discussed. The...

  • Duration of colonization with antimicrobial-resistant bacteria after ICU discharge. Haverkate, Manon; Derde, Lennie; Brun-Buisson, Christian; Bonten, Marc; Bootsma, Martin // Intensive Care Medicine;Apr2014, Vol. 40 Issue 4, p564 

    Purpose: Readmission of patients colonized with antimicrobial-resistant bacteria (AMRB) is important in the nosocomial dynamics of AMRB. We assessed the duration of colonization after discharge from the intensive care unit (ICU) with highly resistant Enterobacteriaceae (HRE),...

  • Acanthamoeba and bacteria produce antimicrobials to target their counterpart. Iqbal, Junaid; Siddiqui, Ruqaiyyah; Ahmed Khan, Naveed // Parasites & Vectors;2014, Vol. 7 Issue 1, p1 

    Background In the microbial ecosystem, microbes compete for space and nutrients. Consequently, some have developed the ability to kill or inhibit the growth of other competing microbes by producing antimicrobial substances. As the 'producer' species are generally immune to these substances,...

  • Global network analysis of drug tolerance, mode of action and virulence in methicillin-resistant S. aureus. Overton, Ian M.; Graham, Shirley; Gould, Katherine A.; Hinds, Jason; Botting, Catherine H.; Shirran, Sally; Barton, Geoffrey J.; Coote, Peter J. // BMC Systems Biology;2011, Vol. 5 Issue 1, p68 

    Background: Staphylococcus aureus is a major human pathogen and strains resistant to existing treatments continue to emerge. Development of novel treatments is therefore important. Antimicrobial peptides represent a source of potential novel antibiotics to combat resistant bacteria such as...

Share

Read the Article

Courtesy of THE LIBRARY OF VIRGINIA

Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics