Ultrastructural, metabolic and genetic characteristics of determinants facilitating the acquisition of macrolide resistance by Streptococcus pneumoniae.
Xueqing Wu, Babek Alibayov, Xi Xiang, Santiago M Lattar, Fuminori Sakai, Austin A Medders, Brenda S Antezana, Lance E Keller, Ana G J Vidal, Yih-Ling Tzeng, D Ashley Robinson, David S Stephens, Yunsong Yu, Jorge E Vidal
Author Information
Xueqing Wu: Department of Infectious Diseases, Regional Medical Center for National Institute of Respiratory Diseases, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310052, China; Key Laboratory of Microbial Technology and Bioinformatics of Zhejiang Province, Hangzhou 310052, China.
Babek Alibayov: Center for Immunology and Microbial Research, University of Mississippi Medical Center, Jackson, MS 39216, United States.
Xi Xiang: Department of Clinical Laboratory, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua 321000, China.
Santiago M Lattar: Hubert Department of Global Health, Rollins School of Public Health, Emory University, Atlanta, GA 30322, United States.
Fuminori Sakai: Hubert Department of Global Health, Rollins School of Public Health, Emory University, Atlanta, GA 30322, United States.
Austin A Medders: Department of Cell and Molecular Biology, University of Mississippi Medical Center, Jackson, MS 39216, United States.
Brenda S Antezana: Department of Medicine, School of Medicine, Emory University, Atlanta, GA 30322, United States; Graduate Program in Microbiology and Molecular Genetics, Emory University, Atlanta, GA 30322, United States.
Lance E Keller: Department of Cell and Molecular Biology, University of Mississippi Medical Center, Jackson, MS 39216, United States; Center for Immunology and Microbial Research, University of Mississippi Medical Center, Jackson, MS 39216, United States.
Ana G J Vidal: Department of Cell and Molecular Biology, University of Mississippi Medical Center, Jackson, MS 39216, United States.
Yih-Ling Tzeng: Department of Medicine, School of Medicine, Emory University, Atlanta, GA 30322, United States; Graduate Program in Microbiology and Molecular Genetics, Emory University, Atlanta, GA 30322, United States.
D Ashley Robinson: Department of Cell and Molecular Biology, University of Mississippi Medical Center, Jackson, MS 39216, United States; Center for Immunology and Microbial Research, University of Mississippi Medical Center, Jackson, MS 39216, United States.
David S Stephens: Department of Medicine, School of Medicine, Emory University, Atlanta, GA 30322, United States; Graduate Program in Microbiology and Molecular Genetics, Emory University, Atlanta, GA 30322, United States.
Yunsong Yu: Department of Infectious Diseases, Regional Medical Center for National Institute of Respiratory Diseases, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310052, China; Key Laboratory of Microbial Technology and Bioinformatics of Zhejiang Province, Hangzhou 310052, China. Electronic address: yvys119@zju.edu.cn.
Jorge E Vidal: Department of Cell and Molecular Biology, University of Mississippi Medical Center, Jackson, MS 39216, United States; Center for Immunology and Microbial Research, University of Mississippi Medical Center, Jackson, MS 39216, United States. Electronic address: jvidal@umc.edu.
AIMS: To investigate the molecular events associated with acquiring macrolide resistance genes [mefE/mel (Mega) or ermB] in Streptococcus pneumoniae (Spn) during nasopharyngeal colonization. METHODS AND RESULTS: Genomic analysis of 128 macrolide-resistant Spn isolates revealed recombination events in genes of the conjugation apparatus, or the competence system, in strains carrying Tn916-related elements. Studies using confocal and electron microscopy demonstrated that during the transfer of Tn916-related elements in nasopharyngeal cell biofilms, pneumococcal strains formed clusters facilitating their acquisition of resistance determinants at a high recombination frequency (rF). Remarkably, these aggregates comprise both encapsulated and nonencapsulated pneumococci that span extracellular and intracellular compartments. rF assessments showed similar rates regardless Mega was associated with large integrative and conjugative elements (ICEs) (>23���kb) or not (���5.4���kb). The rF for Mega Class IV(c) insertion region (���53���kb) was three orders of magnitude higher than the transformation of the capsule locus. Metabolomics studies of the microenvironment created by colonization of human nasopharyngeal cells revealed a link between the acquisition of ICEs and the pathways involving nicotinic acid and sucrose. CONCLUSIONS: Pneumococcal clusters, both extracellular and intracellular, facilitate macrolide resistance acquisition, and ICEs were acquired at a higher frequency than the capsule locus. Metabolic changes could serve as intervention targets.
References
Appl Environ Microbiol. 2017 Aug 1;83(16):
[PMID: 28576759]
