PMID- 27303749
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20160615
LR  - 20181113
IS  - 2379-5042 (Print)
IS  - 2379-5042 (Electronic)
IS  - 2379-5042 (Linking)
VI  - 1
IP  - 3
DP  - 2016 May-Jun
TI  - CRISPR-Cas and Restriction-Modification Act Additively against Conjugative 
      Antibiotic Resistance Plasmid Transfer in Enterococcus faecalis.
LID - 10.1128/mSphere.00064-16 [doi]
LID - e00064-16
AB  - Enterococcus faecalis is an opportunistic pathogen and a leading cause of 
      nosocomial infections. Conjugative pheromone-responsive plasmids are 
      narrow-host-range mobile genetic elements (MGEs) that are rapid disseminators of 
      antibiotic resistance in the faecalis species. Clustered regularly interspaced 
      short palindromic repeat (CRISPR)-Cas and restriction-modification confer 
      acquired and innate immunity, respectively, against MGE acquisition in bacteria. 
      Most multidrug-resistant E. faecalis isolates lack CRISPR-Cas and possess an 
      orphan locus lacking cas genes, CRISPR2, that is of unknown function. Little is 
      known about restriction-modification defense in E. faecalis. Here, we explore the 
      hypothesis that multidrug-resistant E. faecalis strains are immunocompromised. We 
      assessed MGE acquisition by E. faecalis T11, a strain closely related to the 
      multidrug-resistant hospital isolate V583 but which lacks the ~620 kb of 
      horizontally acquired genome content that characterizes V583. T11 possesses the 
      E. faecalis CRISPR3-cas locus and a predicted restriction-modification system, 
      neither of which occurs in V583. We demonstrate that CRISPR-Cas and 
      restriction-modification together confer a 4-log reduction in acquisition of the 
      pheromone-responsive plasmid pAM714 in biofilm matings. Additionally, we show 
      that the orphan CRISPR2 locus is functional for genome defense against another 
      pheromone-responsive plasmid, pCF10, only in the presence of cas9 derived from 
      the E. faecalis CRISPR1-cas locus, which most multidrug-resistant E. faecalis 
      isolates lack. Overall, our work demonstrated that the loss of only two loci led 
      to a dramatic reduction in genome defense against a clinically relevant MGE, 
      highlighting the critical importance of the E. faecalis accessory genome in 
      modulating horizontal gene transfer. Our results rationalize the development of 
      antimicrobial strategies that capitalize upon the immunocompromised status of 
      multidrug-resistant E. faecalis. IMPORTANCE Enterococcus faecalis is a bacterium 
      that normally inhabits the gastrointestinal tracts of humans and other animals. 
      Although these bacteria are members of our native gut flora, they can cause 
      life-threatening infections in hospitalized patients. Antibiotic resistance genes 
      appear to be readily shared among high-risk E. faecalis strains, and multidrug 
      resistance in these bacteria limits treatment options for infections. Here, we 
      find that CRISPR-Cas and restriction-modification systems, which function as 
      adaptive and innate immune systems in bacteria, significantly impact the spread 
      of antibiotic resistance genes in E. faecalis populations. The loss of these 
      systems in high-risk E. faecalis suggests that they are immunocompromised, a 
      tradeoff that allows them to readily acquire new genes and adapt to new 
      antibiotics.
FAU - Price, Valerie J
AU  - Price VJ
AD  - Department of Biological Sciences, The University of Texas at Dallas, Richardson, 
      Texas, USA.
FAU - Huo, Wenwen
AU  - Huo W
AD  - Department of Biological Sciences, The University of Texas at Dallas, Richardson, 
      Texas, USA.
FAU - Sharifi, Ardalan
AU  - Sharifi A
AD  - Department of Biological Sciences, The University of Texas at Dallas, Richardson, 
      Texas, USA.
FAU - Palmer, Kelli L
AU  - Palmer KL
AUID- ORCID: 0000-0002-7343-9271
AD  - Department of Biological Sciences, The University of Texas at Dallas, Richardson, 
      Texas, USA.
LA  - eng
GR  - K22 AI099088/AI/NIAID NIH HHS/United States
GR  - R01 AI116610/AI/NIAID NIH HHS/United States
PT  - Journal Article
DEP - 20160601
PL  - United States
TA  - mSphere
JT  - mSphere
JID - 101674533
CIN - mSphere. 2016 May-Jun;1(3). pii: e00127-16. doi: 10.1128/mSphere.00127-16. PMID: 
      27306929
PMC - PMC4894674
OTO - NOTNLM
OT  - CRISPR
OT  - Enterococcus
OT  - antibiotic resistance
OT  - horizontal gene transfer
OT  - plasmids
EDAT- 2016/06/16 06:00
MHDA- 2016/06/16 06:01
PMCR- 2016/06/01
CRDT- 2016/06/16 06:00
PHST- 2016/03/08 00:00 [received]
PHST- 2016/04/12 00:00 [accepted]
PHST- 2016/06/16 06:00 [entrez]
PHST- 2016/06/16 06:00 [pubmed]
PHST- 2016/06/16 06:01 [medline]
PHST- 2016/06/01 00:00 [pmc-release]
AID - mSphere00064-16 [pii]
AID - 10.1128/mSphere.00064-16 [doi]
PST - epublish
SO  - mSphere. 2016 Jun 1;1(3):e00064-16. doi: 10.1128/mSphere.00064-16. eCollection 
      2016 May-Jun.