Biology subjects

Goodman, R. N.

Publications and source records attributed to Goodman, R. N..

4 recordsLinked to original sources

bioRxiv2025

From Colonisation to Invasion: Genomic and Phenotypic Comparison of Faecal and Bloodstream Isolates from the same patients

Gram-negative bloodstream infections (GNBSI) carry a significant global health burden. Escherichia coli and Klebsiella pneumoniae are the two most common causes of healthcare-associated GNBSI, which may arise from gastrointestinal tract (GIT) colonisation. Understanding genomic and phenotypic adaptations that underpin transition from GIT colonisation to invasive bloodstream infection could improve understanding of pathogenesis. This study identified linked faecal and blood isolates from children with healthcare-associated GNBSI caused by E. coli and K. pneumoniae. Linked pairs were compared for antimicrobial resistance, biofilm formation, and underwent comparative genomic analysis via whole-genome sequencing, comparative average nucleotide identity (ANI) and core genome single nucleotide polymorphism (SNP) analysis. Five isolate pairs (three E. coli, two K. pneumoniae) showed high relatedness, supporting GIT origin of bloodstream infection. Isolates within pairs had identical virulence genes whereas phenotypic assays revealed changes in antimicrobial susceptibility, with one pair undergoing changes in resistance gene profiles, and increased biofilm formation in 4/5 isolates. This study provides insight into within-host evolution from gastrointestinal colonisation to bloodstream invasion in Gram-negative pathogens. Convergence on metabolic adaptation and biofilm formation suggests these traits may be advantageous in healthcare-associated GNBSI. Further studies involving larger cohorts alongside functional validation of mutations are needed to better understand GNBSI pathogenesis.

microbiology↗

bioRxiv2025

Shotgun metagenomic analysis of the oral microbiomes of children with noma reveals a novel disease-associated organism

Noma is a rapidly progressive orofacial gangrene that predominantly affects children living in extreme poverty. Despite its documentation since antiquity and its designation as a World Health Organisation Neglected Tropical Disease in 2023, the microbiological cause of noma remains poorly understood, with no specific organisms confidently identified as definitive aetiological agents. Here, we present the first deep shotgun metagenomic profiling of oral saliva microbiomes from 19 Nigerian children with acute noma. Our analyses reveal marked microbial dysbiosis in noma microbiomes, with machine learning and multivariate statistical analyses indicating significant enrichment of Treponema, Porphyromonas, and Bacteroides, alongside depletion of Streptococcus and Rothia, as key microbial signatures of noma disease. From the dataset we recovered 40 high-quality Treponema metagenome-assembled genomes (MAGs) spanning 19 species, 14 of which were novel. Notably, a novel species designated Treponema sp. A was detected in 15 of the 19 noma participants and was entirely absent from global healthy saliva metagenomes. Re-analysis of previously published 16S rRNA datasets from children with noma in Niger also revealed Treponema sp. A to be highly prevalent in noma cases but rare in controls. This study identifies Treponema--particularly Treponema sp. A--as a strong candidate organism associated with noma pathogenesis. Additionally, analysis of antimicrobial resistance determinants detected in noma metagenomes revealed concerning levels of resistance to antibiotics commonly used in noma treatment, particularly {beta}-lactams and metronidazole, especially among Prevotella species. These findings provide the first high-resolution microbial framework for noma and offer a foundation for future research into its pathogenesis and the development of novel diagnostics, therapeutics, and preventive strategies in endemic settings.

pathology↗

bioRxiv2025

Genomic comparison of highly related pairs of E. coli and K. pneumoniae isolated from faeces and blood of the same neonatal patients hospitalized with fever in Dar es Salaam, Tanzania

Blood stream infections (BSIs) are a major cause of hospitalisation and death for children under the age of five in sub-Saharan Africa with members of the Gram-negative bacteria Enterobacterales such as Klebsiella pneumoniae and Escherichia coli among the most common causative agents. These bacteria usually colonise the human gastrointestinal (GI) tract which has been identified as a reservoir for invasive infections into extra-intestinal environments such as the urinary tract and bloodstream. In this study we used comparative genomics to compare hybrid genome assemblies of blood and faecal isolates taken from the same patients (all neonates under 19 days old) to determine if the BSI associated bacterial isolates originated in their GI tract. We show that both E. coli and K. pneumoniae likely translocated from the GI tract to the blood in multiple cases of BSI. We also highlight key virulence genes and acquired mutations that are indicative of pathogenic strains capable of BSI. These findings expand our understanding of BSI pathogenesis and could help guide targeted interventions to prevent future BSI infections in neonates.

genomics↗

bioRxiv2023

Molecular mechanisms of re-emerging chloramphenicol susceptibility in extended-spectrum beta-lactamase producing Enterobacterales

Infections with Enterobacterales (E) are increasingly difficult to treat due to antimicrobial resistance. After ceftriaxone replaced chloramphenicol (CHL) as empiric therapy for suspected sepsis in Malawi in 2004, ESBL-E rapidly emerged. Concurrently, resistance to CHL in Escherichia coli and Klebsiella spp. decreased, raising the possibility of CHL re-introduction. However, many phenotypically susceptible isolates still carry CHL acetyltransferase (CAT) genes. We used a combination of genomics, phenotypic susceptibility assays, experimental evolution and functional assays for CAT activity to understand the molecular mechanisms and stability of this re-emerging CHL susceptibility. Of 840 Malawian isolates, 31% had discordant CHL susceptibility genotype-phenotype, and we selected 42 isolates for in-depth analysis. Stable degradation of cat genes by insertion sequences led to re-emergence of CHL susceptibility. Our study suggests CHL could be reintroduced as reserve agent for critically ill patients with ESBL-E infections in Malawi and similar settings and highlights the ongoing challenges in inferring antimicrobial resistance from sequence data.

microbiology↗