title: Oral cavities of healthy infants harbour high proportions of Streptococcus salivarius strains with phenotypic and genotypic resistance to multiple classes of antibiotics.
abstract: Emerging antibiotic resistance in the oropharyngeal microbiota, of which Streptococcus salivarius is a prominent species, represents a challenge for treating paediatric populations. In this study, we investigated the role of Streptococcussalivarius as a reservoir for antibiotic resistance genes (ARG) in the oral microbiota by analysing 95 Streptococcussalivarius isolates from 22 healthy infants (2-16 months of age). MICs of penicillin G, amoxicillin, erythromycin, tetracycline, doxycycline and streptomycin were determined. ARG profiles were assessed in a subset of 21 strains by next-generation sequencing of genomes, followed by searches of assembled reads against the Comprehensive Antibiotic Resistance Database. Strains resistant to erythromycin, penicillins and tetracyclines were isolated from 83.3, 33.3 and 16.6 %, respectively, of infants aged 2 to 8 months with no prior antibiotic treatment. These percentages were100.0, 66.6 and 50.0 %, by 13 to 16 months of age. ARG or polymorphisms associated with antibiotic resistance were the most prevalent and involved genes for macrolide efflux (mel, mefA/E and macB), ribosomal protection [erm(B), tet(M) and tet(O)] and β-lactamase-like proteins. Phylogenetically related strains showing multidrug-resistant phenotypes harboured multidrug efflux ARG. Polymorphic genes associated with antibiotic resistance to drugs affecting DNA replication, folate synthesis, RNA/protein synthesis and regulators of antibiotic stress responses were detected. These data imply that Streptococcussalivarius strains established during maturation of the oral microbiota harbour a diverse array of functional ARG, even in the absence of antibiotic selective pressures, highlighting a potential role for this species in shaping antibiotic susceptibility profiles of oropharyngeal communities.
authors.affiliation: Department of Oral Diagnosis, University of Campinas, São Paulo, Brazil.
authors.forename: Thaís H
authors.initials: TH
authors.lastname: Palma
authors.affiliation: Department of Oral Diagnosis, University of Campinas, São Paulo, Brazil.
authors.forename: Erika N
authors.initials: EN
authors.lastname: Harth-Chú
authors.affiliation: Department of Microbiology, The Forsyth Institute, Cambridge, MA, USA.
authors.forename: Jodie
authors.initials: J
authors.lastname: Scott
authors.affiliation: Department of Oral Diagnosis, University of Campinas, São Paulo, Brazil.
authors.forename: Rafael N
authors.initials: RN
authors.lastname: Stipp
authors.affiliation: Department of Microbiology, The Forsyth Institute, Cambridge, MA, USA.
authors.forename: Heike
authors.initials: H
authors.lastname: Boisvert
authors.affiliation: Piracicaba Dental School, University of Campinas, São Paulo, Brazil.
authors.forename: Mariana F
authors.initials: MF
authors.lastname: Salomão
authors.affiliation: Department of Oral Diagnosis, University of Campinas, São Paulo, Brazil.
authors.forename: Jéssica D
authors.initials: JD
authors.lastname: Theobaldo
authors.affiliation: Cepae - Research and Dental Care Center for Special Needs Patients of Piracicaba Dental School, University of Campinas, São Paulo, Brazil.
authors.forename: Rosana F
authors.initials: RF
authors.lastname: Possobon
authors.affiliation: Laboratory of Genomics and Gene Expression (LGE), University of Campinas, São Paulo, Brazil.
authors.forename: Leandro C
authors.initials: LC
authors.lastname: Nascimento
authors.affiliation: Department of Microbiology, The Forsyth Institute, Cambridge, MA, USA.
authors.forename: Jonathan W
authors.initials: JW
authors.lastname: McCafferty
authors.affiliation: Department of Microbiology, The Forsyth Institute, Cambridge, MA, USA.
authors.forename: Lina
authors.initials: L
authors.lastname: Faller
authors.affiliation: Department of Microbiology, The Forsyth Institute, Cambridge, MA, USA.
authors.forename: Margaret J
authors.initials: MJ
authors.lastname: Duncan
authors.affiliation: Department of Oral Diagnosis, University of Campinas, São Paulo, Brazil.
authors.forename: Renata O
authors.initials: RO
authors.lastname: Mattos-Graner
mesh_terms: D000900:Anti-Bacterial Agents / Q000145:classification / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics; D005260:Female; D005798:Genes, Bacterial; D019450:Genes, MDR; D016680:Genome, Bacterial; D005838:Genotype; D064368:Healthy Volunteers; D006801:Humans; D007223:Infant; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D008826:Microbial Sensitivity Tests; D009055:Mouth / Q000382:microbiology*; D010641:Phenotype; D017422:Sequence Analysis, DNA; D000070001:Streptococcus salivarius / Q000145:classification / Q000187:drug effects* / Q000235:genetics* / Q000502:physiology
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D002352:Carrier Proteins; C117866:MefA protein, Streptococcus; D008565:Membrane Proteins; C083139:Tet O resistance protein, Bacteria