PMID- 30483235
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220409
IS  - 1664-302X (Print)
IS  - 1664-302X (Electronic)
IS  - 1664-302X (Linking)
VI  - 9
DP  - 2018
TI  - Factors Contributing to the Evolution of mecA-Mediated beta-lactam Resistance in 
      Staphylococci: Update and New Insights From Whole Genome Sequencing (WGS).
PG  - 2723
LID - 10.3389/fmicb.2018.02723 [doi]
LID - 2723
AB  - The understanding of the mechanisms of antibiotic resistance development are 
      fundamental to alert and preview beforehand, the large scale dissemination of 
      resistance to antibiotics, enabling the design of strategies to prevent its 
      spread. The mecA-mediated methicillin resistance conferring resistance to 
      broad-spectrum beta-lactams is globally spread in staphylococci including hospitals, 
      farms and community environments, turning ineffective the most widely used and 
      efficient class of antibiotics to treat staphylococcal infections. The use of 
      whole genome sequencing (WGS) technologies at a bacterial population level has 
      provided a considerable progress in the identification of key steps that led to 
      mecA-mediated beta-lactam resistance development and dissemination. Data obtained 
      from multiple studies indicated that mecA developed from a harmless core gene 
      (mecA1) encoding the penicillin-binding protein D (PbpD) from staphylococcal 
      species of animal origin (S. sciuri group) due to extensive beta-lactams use in 
      human created environments. Emergence of the resistance determinant involved 
      distortion of PbpD active site, increase in mecA1 expression, addition of 
      regulators (mecR1, mecI) and integration into a mobile genetic element (SCCmec). 
      SCCmec was then transferred into species of coagulase-negative staphylococci 
      (CoNS) that are able to colonize both animals and humans and subsequently 
      transferred to S. aureus of human origin. Adaptation of S. aureus to the 
      exogenously acquired SCCmec involved, deletion and mutation of genes implicated 
      in general metabolism (auxiliary genes) and general stress response and the 
      adjustment of metabolic networks, what was accompanied by an increase in 
      beta-lactams minimal inhibitory concentration and the transition from a 
      heterogeneous to homogeneous resistance profile. Nowadays, methicillin-resistant 
      S. aureus (MRSA) carrying SCCmec constitutes one of the most important worldwide 
      pandemics. The stages of development of mecA-mediated beta-lactam resistance 
      described here may serve as a model for previewing and preventing the emergence 
      of resistance to other classes of antibiotics.
FAU - Miragaia, Maria
AU  - Miragaia M
AD  - Laboratory of Bacterial Evolution and Molecular Epidemiology, Instituto de 
      Tecnologia Quimica e Biologica Antonio Xavier, Universidade Nova de Lisboa, 
      Oeiras, Portugal.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20181113
PL  - Switzerland
TA  - Front Microbiol
JT  - Frontiers in microbiology
JID - 101548977
PMC - PMC6243372
OTO - NOTNLM
OT  - Staphylococcus sciuri
OT  - methicillin-resistant Staphylococcus aureus (MRSA)
OT  - staphylococcal cassette chromosome mec (SCCmec)
OT  - whole genome sequencing
OT  - beta-lactams resistance
EDAT- 2018/11/30 06:00
MHDA- 2018/11/30 06:01
PMCR- 2018/11/13
CRDT- 2018/11/29 06:00
PHST- 2018/05/14 00:00 [received]
PHST- 2018/10/24 00:00 [accepted]
PHST- 2018/11/29 06:00 [entrez]
PHST- 2018/11/30 06:00 [pubmed]
PHST- 2018/11/30 06:01 [medline]
PHST- 2018/11/13 00:00 [pmc-release]
AID - 10.3389/fmicb.2018.02723 [doi]
PST - epublish
SO  - Front Microbiol. 2018 Nov 13;9:2723. doi: 10.3389/fmicb.2018.02723. eCollection 
      2018.