Longitudinal changes in the nasopharyngeal resistome of South African infants using shotgun metagenomic sequencing

Manenzhe, Rendani I.; Dube, Felix S.; Wright, Meredith S.; Lennard, Katie; Zar, Heather J.; Mounaud, Stephanie; Nierman, William C.; Nicol, Mark P.; Moodley, Clinton

doi:10.1371/journal.pone.0231887

Cited by 11 publications

(10 citation statements)

References 43 publications

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“…However, this was based on the microbiomes of the anterior nares and from an adult population (Human Microbiome Project) [13], which are different from the groups and collection sample sites used in our study. In a recent study focusing on infants, ARGs were detected in 64% of nasopharynx samples [14]. Samples in this study were enriched for streptococci, thus precluding general conclusions on the extent of ARG presence in the natural microbiome.…”

Section: Discussionmentioning

confidence: 92%

The landscape of antibiotic resistance genes in the nasopharynx of preterm infants: Prolonged signature of hospitalization and effects by antibiotics

Dhariwal

Rajar

Salvadori

et al. 2023

Preprint

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Respiratory infections caused by common pathogens that colonize the respiratory tract, including the nasopharynx, are a leading global cause of deaths associated with antimicrobial resistance. Yet, little is known about the antibiotic resistance determinants in the microbial communities of the respiratory tract. In this study, we examined the development of the resistome (collection of antibiotic resistance genes) in the nasopharynx of preterm infants and the impact of early ampicillin plus gentamicin exposure in those requiring broad-spectrum antibiotic treatment for suspected early-onset neonatal sepsis. We analyzed the resistome of 181 nasopharyngeal samples collected longitudinally from 36 preterm infants using deep shotgun metagenomic sequencing. Antibiotic resistance genes were found in most samples (~95%) of both naive and antibiotic-treated infants. We observed a significant increase in the diversity and total abundance of antibiotic resistance genes primarily immediately after early antibiotic therapy. The nasopharyngeal resistome in preterm infants was mainly driven by the microbiome (r = 0.85, p-value = 0.001), with inter-individual differences explaining most of the variation observed in the resistome composition (R2= 30.03%, adjusted p-value = 0.001). We also noted a discernible impact of prenatal maternal antibiotic exposure on the overall resistome composition (R2= 3.6%, adjusted p-value = 0.001), which was observed as a subgroup within the antibiotic-treated group. Overall, these data suggest that the nasopharynx in preterm infants is characterized by a rich resistome with a trajectory that is negatively affected by antibiotics. Although the effects appear to be transient, any adverse changes in resistome during the first days of life bear risks, particularly those selecting for drug resistant colonizers with the potential to spread and cause invasive infections.

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Section: Discussionmentioning

confidence: 92%

The landscape of antibiotic resistance genes in the nasopharynx of preterm infants: Prolonged signature of hospitalization and effects by antibiotics

Dhariwal

Rajar

Salvadori

et al. 2023

Preprint

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“…28 Our study is one of few utilizing shotgun metagenomic sequencing to characterize the nasopharyngeal microbiome during childhood. 29,30 Use of shotgun metagenomic sequencing to characterize respiratory microbial communities presents unique challenges, due in large part to the low microbial biomass in the respiratory tract. Over 99% of the reads generated by this project were human in origin.…”

Section: Discussionmentioning

confidence: 99%

Alterations of the upper respiratory microbiome among children living with HIV infection in Botswana

Patel

Farirai

Patel

et al. 2022

Preprint

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Background. Children living with HIV (CLWH) are at high risk of colonization and infection by bacterial respiratory pathogens. Microbes in the upper respiratory microbiome can prevent colonization by these pathogens. The impact of HIV infection on development of the upper respiratory microbiome during childhood is poorly understood. Methods. We enrolled healthy CLWH (<5 years) and age- and sex-matched HIV-exposed, uninfected (HEU) and HIV-unexposed, uninfected (HUU) children in a cross-sectional study conducted in Botswana. We used shotgun metagenomic sequencing to compare the nasopharyngeal microbiomes of children by HIV status. Findings. Of 143 children, 44 were CLWH, 49 were HEU, and 50 were HUU. Nasopharyngeal microbiome composition differed by HIV status (p=0.043, R2=0.019). The relative abundance of Corynebacterium pseudodiphtheriticum was lower in CLWH compared to HEU and HUU children (p=0.01). Among CLWH, a low (<25%) CD4+ cell percentage was associated with microbiome composition (p=0.009, R2=0.042) and lower relative abundances of Corynebacterium propinquum (p=0.003), C. pseudodiphtheriticum (p=0.007), and Dolosigranulum pigrum (p=0.004). The relative abundances of C. propinquum, C. pseudodiphtheriticum and D. pigrum in the nasopharyngeal microbiome were negatively correlated with the abundances of Streptococcus pneumoniae and Staphylococcus aureus. Interpretation. CLWH with HIV-associated immunosuppression have altered nasopharyngeal microbiome composition and lower abundances of bacterial species associated with respiratory health during childhood. These findings suggest that the upper respiratory microbiome may contribute to the high risk of bacterial respiratory infections among CLWH. Funding. National Institutes of Health, Duke Center for AIDS Research, Penn Center for AIDS Research.

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“…Since NP samples from apparently healthy individuals generally have low numbers of bacterial cells, we used short-term broth enrichment, which has previously been shown to successfully enrich streptococci (31). Since antibiotics may select for resistant strains, the current study used broth enrichment without antibiotics to encourage growth of all S. pneumoniae present without selective pressure (42).…”

Section: Discussionmentioning

confidence: 99%

Characterization of Pneumococcal Colonization Dynamics and Antimicrobial Resistance Using Shotgun Metagenomic Sequencing in Intensively Sampled South African Infants

Manenzhe

Dube

Wright

et al. 2020

Front. Public Health

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Background: There remains a significant proportion of deaths due to pneumococcal pneumonia in infants from low-and middle-income countries despite the marginal global declines recorded in the past decade. Monitoring changes in pneumococcal carriage is key to understanding vaccination-induced shifts in the ecology of carriage, patterns of antimicrobial resistance, and impact on health. We longitudinally investigated pneumococcal carriage dynamics in PCV-13 vaccinated infants by collecting nasopharyngeal (NP) samples at 2-weekly intervals from birth through the first year of life from 137 infants. As a proof of concept, 196 NP samples were retrieved from a subset of 23 infants to explore strain-level pneumococcal colonization patterns and associated antimicrobial-resistance determinants. These were selected on the basis of changes in serotype and antibiogram over time. NP samples underwent short-term enrichment for streptococci prior to total nucleic acid extraction and whole metagenome shotgun sequencing (WMGS). Reads were assembled and aligned to pneumococcal reference genomes for the extraction of pneumococcal and non-pneumococcal bacterial reads. Pneumococcal contigs were aligned to the Antibiotic Resistance Gene-ANNOTation database of acquired AMR genes. In silico pneumococcal capsular and multilocus sequence typing were performed. Results: Of the 196 samples sequenced, 174 had corresponding positive cultures for pneumococci, of which, 152 were assigned an in silico serotype. Metagenomic sequencing detected a single pneumococcal serotype in 85% (129/152), and co-colonization in 15% (23/152) of the samples. Twenty-two different pneumococcal Manenzhe et al. Pneumococcal Colonization Dynamics in a Birth Cohort serotypes were identified, with 15B/15C and 16F being the most common non-PCV13 serotypes, while 23F and 19A were the most common PCV13 serotypes. Twenty-six different sequence types (STs), including four novel STs were identified in silico. Mutations in the folA and folP genes, associated with cotrimoxazole resistance, were detected in 89% (87/98) of cotrimoxazole-non-susceptible pneumococci, as well as in the pbp1a and pbp2x genes, in penicillin non-susceptible ST7052 15B/15C isolates. Conclusions: Metagenomic sequencing of NP samples is a valuable culture-independent technique for a detailed evaluation of the pneumococcal component and resistome of the NP microbiome. This method allowed for the detection of novel STs, as well as co-colonization, with a predominance of non-PCV13 serotypes in this cohort. Forty-eight resistance genes, as well as mutations associated with resistance were detected, but the correlation with phenotypic non-susceptibility was lower than expected.

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Longitudinal changes in the nasopharyngeal resistome of South African infants using shotgun metagenomic sequencing

Cited by 11 publications

References 43 publications

The landscape of antibiotic resistance genes in the nasopharynx of preterm infants: Prolonged signature of hospitalization and effects by antibiotics

The landscape of antibiotic resistance genes in the nasopharynx of preterm infants: Prolonged signature of hospitalization and effects by antibiotics

Alterations of the upper respiratory microbiome among children living with HIV infection in Botswana

Characterization of Pneumococcal Colonization Dynamics and Antimicrobial Resistance Using Shotgun Metagenomic Sequencing in Intensively Sampled South African Infants

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