- Volume 10, Issue 12, 2024

Because large brains are energetically expensive, they are associated with metabolic traits that facilitate energy availability across vertebrates. However, the biological underpinnings driving these traits are not known. Given its role in regulating host metabolism in disease studies, we hypothesized that the gut microbiome contributes to variation in normal cross-vertebrate species differences in metabolism, including those associated with the brain’s energetic requirements. By inoculating germ-free mice with the gut microbiota (GM) of three primate species – two with relatively larger brains and one with a smaller brain – we demonstrated that the GM of larger-brained primates shifts host metabolism towards energy use and production, while that of smaller-brained primates stimulates energy storage in adipose tissues. Our findings establish a causal role of the GM in normal cross-host species differences in metabolism associated with relative brain size and suggest that the GM may have been an important facilitator of metabolic changes during human evolution that supported encephalization.

Streptococcus suis is a Gram-positive opportunistic pathogen causing systemic disease in piglets around weaning age. The factors predisposing to disease are not known. We hypothesized that the tonsillar microbiota might influence disease risk via colonization resistance and/or co-infections. We conducted a cross-sectional case–control study within outbreak farms complemented by selective longitudinal sampling and comparison with control farms without disease occurrence. We found a small but significant difference in tonsil microbiota composition between case and control piglets (n=45+45). Variants of putative commensal taxa, including Rothia nasimurium, were reduced in abundance in case piglets compared to asymptomatic controls. Case piglets had higher relative abundances of Fusobacterium gastrosuis, Bacteroides heparinolyticus and uncultured Prevotella and Alloprevotella species. Piglets developing disease post-weaning had reduced alpha diversity pre-weaning. Despite case–control pairs receiving equal antimicrobial treatment, case piglets had a higher abundance of antimicrobial resistance genes conferring resistance to antimicrobial classes used to treat S. suis. This might be an adaption of disease-associated strains to frequent antimicrobial treatment.

Antimicrobial resistance (AMR) gene cassettes comprise an AMR gene flanked by short recombination sites (attI and attC or attC and attC). Integrons are genetic elements able to capture, excise and shuffle these cassettes, providing ‘adaptation on demand’, and can be found on both chromosomes and plasmids. Understanding the patterns of integron diversity may help to understand the epidemiology of AMR genes. As a case study, we examined the clinical resistance gene bla GES-5, an integron-associated class A carbapenemase first reported in Greece in 2004 and since observed worldwide, which to our knowledge has not been the subject of a previous global analysis. Using a dataset comprising all de-duplicated NCBI contigs containing bla GES-5 (n=104), we developed a pangenome graph-based workflow to characterize and cluster the diversity of bla GES-5-associated integrons. We demonstrate that bla GES-5-associated integrons on plasmids are different to those on chromosomes. Chromosomal integrons were almost all identified in Pseudomonas aeruginosa ST235, with a consistent gene cassette content and order. We observed instances where insertion sequence IS110 disrupted attC sites, which might immobilize the gene cassettes and explain the conserved integron structure despite the presence of intI1 integrase promoters, which would typically facilitate capture or excision and rearrangement. The plasmid-associated integrons were more diverse in their gene cassette content and order, which could be an indication of greater integrase activity and ‘shuffling’ of integrons on plasmids.

Zoonotic pathogen transmission is of growing concern globally, with agricultural intensification facilitating interactions between humans, livestock and wild animals. Staphylococcus aureus is a major human pathogen, but it also causes mastitis in dairy cattle, leading to an economic burden on the dairy industry. Here, we investigated transmission within and between cattle and humans, including potential zoonotic transmission of S. aureus isolated from cattle and humans from three dairy farms and an associated primary school in New Zealand. Nasal swabs (N=170) were taken from healthy humans. Inguinal and combined nasal/inguinal swabs were taken from healthy cattle (N=1163). Whole-genome sequencing was performed for 96 S. aureus isolates (44 human and 52 cattle). Multilocus sequence typing and assessments of antimicrobial resistance and virulence were carried out. Potential within- and across-species transmission events were determined based on single nucleotide polymorphisms (SNPs). Thirteen potential transmission clusters were detected, with 12 clusters restricted to within-species and one potential zoonotic transmission cluster (ST5). Potential transmission among cattle was mostly limited to single age groups, likely because different age groups are managed separately on farms. While the prevalence of antimicrobial resistance (AMR) was low among both bovine and human isolates, the discovery of an extended-spectrum beta-lactamase gene (bla TEM-116) in a bovine isolate was concerning. This study provides evidence around frequency and patterns of potential transmission of S. aureus on dairy farms and highlights the AMR and virulence profile of asymptomatic carriage S. aureus isolates.

Methicillin-resistant Staphylococcus aureus (MRSA) is a common cause of infection in both community and healthcare settings, and the household may be a central component linking these two environments. Strategies to prevent S. aureus transmission and thereby reduce the risk of infection must be informed by a detailed understanding of local epidemiology. These data are typically lacking in many low- and middle-income countries. Therefore, we aimed to investigate the circulation of infecting S. aureus strains in Sri Lanka, with a focus on the community and healthcare interface. A prospective longitudinal cohort study was performed between July and December 2021. Index patients with S. aureus infection and up to four of their household contacts were enrolled in the study. Colonization was assessed by sampling participants’ nose and axilla at two time points over 3 months of follow-up. Whole-genome sequencing (WGS) was used to characterize isolates and assess strain similarity to identify transmission episodes and environmental clusters. A total of 153 participants were recruited, including 42 S. aureus-positive index patients and 111 household contacts. The baseline prevalence of S. aureus colonization amongst household contacts was 11.7% (13/111), of which 30.8% (4/13) were methicillin-resistant. A total of 88 S. aureus isolates underwent WGS and three multilocus sequence types predominated: ST672, ST5 and ST6. Each type had unique virulence characteristics but was identified in both community and healthcare environments. Colonization of household members with the index’s infecting strain was not detected. S. aureus is a major cause of morbidity and mortality in low-resource settings such as Sri Lanka, yet little is known about risk factors and transmission networks. In this descriptive study, we have identified a small number of strains that appear to be well established and capable of causing both severe infection and asymptomatic colonization. Transmission of S. aureus did not appear to be occurring frequently in the household, and, therefore, preventative strategies that target high-risk groups may be more successful than universal community-based measures.

Non-toxigenic non-O1/non-O139 Vibrio cholerae (NVC) isolates are associated with diarrhoeal disease globally. NVC-related infections are on the rise, representing one of the most striking examples of emerging human diseases linked to climate change. This study aims to give a better picture of the evolution of NCV incidence in Spain from 2012 to 2022. In this context, we realized a descriptive analysis and a logistic regression using the isolates submitted to the National Center of Microbiology (NCM) during this period. To elucidate the heterogeneity of sporadic clinical strains of NVC among patients residing in Spain, we conducted whole-genome sequencing (WGS) of a selection of isolates. First, we observed an increase in the number of isolates sent to the NCM after 2019, which was not concomitant to a change in the national surveillance protocol. Furthermore, the number of cases and hospitalizations increased with age. Second, we found a high diversity of NVC strains, which suggested that the usefulness of WGS studies might be limited in waterborne outbreak situations to find the infectious source. Finally, we characterized the genetic determinants responsible for antimicrobial resistance and virulence and found that 21% of the isolates were resistant to β-lactamases. To the best of our knowledge, the present study is the first in Spain to report genomic data on non-toxigenic cases at the national level. Because of the high percentage of hospitalization observed for NVC cases (40%), it might be beneficial to test for V. cholerae in all the suspected cases.