Ultrastructural, Metabolic and Genetic Characteristics of Determinants Facilitating the Acquisition of Macrolide Resistance by Streptococcus Pneumoniae

Overview

Journal Drug Resist Updat

Specialties Infectious Diseases
Oncology

Date 2024 Aug 21

PMID 39167981

Authors

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

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

Fluorescent antibody-based detection and ultrastructural analysis of Streptococcus pneumoniae in human sputum.

Vidal A, Francis M, Chitanvis M, Takeshita K, Frame I, Sharma P Pneumonia (Nathan). 2025; 17(1):4.

PMID: 40038770 PMC: 11881295. DOI: 10.1186/s41479-025-00157-z.

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