Fast exact gap-affine partial order alignment with POASTA.

Motivation: Partial order alignment is a widely used method for computing multiple sequence alignments, with applications in genome assembly and pangenomics, among many others. Current algorithms to compute the optimal, gap-affine partial order alignment do not scale well to larger graphs and sequences. While heuristic approaches exist, they do not guarantee optimal alignment and sacrifice alignment accuracy.

Clinical and genomic characterization of Klebsiella pneumoniae infections in Dhaka, Bangladesh.

Background: Klebsiella pneumoniae (Kpn), a WHO priority pathogen with high rates of antimicrobial resistance (AMR), has emerged as a leading cause of hospital acquired pneumonia and neonatal sepsis.

Objective: We aimed to define the clinical characteristics of a cohort of patients with Kpn infection in Dhaka, Bangladesh and to perform phenotypic and genetic characterization of the associated isolates.

Methods: We retrospectively extracted clinical data about patients at Dhaka Medical College Hospital from whom Klebsiella spp was isolated from a clinical specimen collected between February and September 2022.

Effects of commonly used antibiotics on children's developing gut microbiomes and resistomes in peri-urban Lima, Peru.

Background: The effects of antibiotic use on children's gut microbiomes and resistomes are not well characterized in middle-income countries, where pediatric antibiotic consumption is exceptionally common. We characterized the effects of antibiotics commonly used by Peruvian children (i.e.

Distinct Escherichia coli transcriptional profiles in the guts of recurrent UTI sufferers revealed by pangenome hybrid selection.

Low-abundance members of microbial communities are difficult to study in their native habitats, including Escherichia coli, a minor but common inhabitant of the gastrointestinal tract, and key opportunistic pathogen of the urinary tract. While multi-omic analyses have detailed interactions between uropathogenic Escherichia coli (UPEC) and the bladder mediating urinary tract infection (UTI), little is known about UPEC in its pre-infection reservoir, the gastrointestinal tract, partly due to its low relative abundance (<1%). To sensitively explore the genomes and transcriptomes of diverse gut E.

Rapid Emergence of Resistance to Broad-Spectrum Direct Antimicrobial Activity of Avibactam.

Avibactam (AVI) is a diazabicyclooctane (DBO) β-lactamase inhibitor used clinically in combination with ceftazidime. At concentrations higher than those typically achieved , it also has broad-spectrum direct antibacterial activity against strains, including metallo-β-lactamase-producing isolates, mediated by inhibition of penicillin-binding protein 2 (PBP2). This activity is mechanistically similar to that of more potent novel DBOs (zidebactam, nacubactam) in late clinical development.

Dynamics of microbiome and resistome in a poultry burger processing line.

Traditionally, surveillance programs for food products and food processing environments have focused on targeted pathogens and resistance genes. Recent advances in high throughput sequencing allow for more comprehensive and untargeted monitoring. This study assessed the microbiome and resistome in a poultry burger processing line using culturing techniques and whole metagenomic sequencing (WMS).

Bacterial strain sharing between humans, animals, and the environment among urban households.

Identifying bacterial transmission pathways is crucial to inform strategies aimed at curbing the spread of pathogenic and antibiotic-resistant bacteria, especially in rapidly urbanizing low- and middle-income countries. In this study, we assessed bacterial strain-sharing and dissemination of antibiotic resistance across humans, domesticated poultry, canines, household soil, and drinking water in urban informal settlements in Nairobi, Kenya. We collected 321 samples from 50 households and performed Pooling Isolated Colonies-seq (PIC-seq) by sequencing pools of up to five colonies per sample to capture strain diversity, strain-sharing patterns, and overlap of antibiotic-resistant genes (ARGs).

Distinct transcriptional profiles in the guts of recurrent UTI sufferers revealed by pangenome hybrid selection.

Low-abundance members of microbial communities are difficult to study in their native habitats. This includes , a minor, but common inhabitant of the gastrointestinal tract and opportunistic pathogen, including of the urinary tract, where it is the primary pathogen. While multi-omic analyses have detailed critical interactions between uropathogenic (UPEC) and the bladder that mediate UTI outcome, comparatively little is known about UPEC in its pre-infection reservoir, partly due to its low abundance there (<1% relative abundance).

Persistent Salmonella infections in humans are associated with mutations in the BarA/SirA regulatory pathway.

Several bacterial pathogens, including Salmonella enterica, can cause persistent infections in humans by mechanisms that are poorly understood. By comparing genomes of isolates longitudinally collected from 256 prolonged salmonellosis patients, we identified repeated mutations in global regulators, including the barA/sirA two-component regulatory system, across multiple patients and Salmonella serovars. Comparative RNA-seq analysis revealed that distinct mutations in barA/sirA led to diminished expression of Salmonella pathogenicity islands 1 and 4 genes, which are required for Salmonella invasion and enteritis.

Discovery of a structural class of antibiotics with explainable deep learning.

The discovery of novel structural classes of antibiotics is urgently needed to address the ongoing antibiotic resistance crisis. Deep learning approaches have aided in exploring chemical spaces; these typically use black box models and do not provide chemical insights. Here we reasoned that the chemical substructures associated with antibiotic activity learned by neural network models can be identified and used to predict structural classes of antibiotics.

Utility of Mycobacterium tuberculosis Genome Sequencing Snapshots to Assess Transmission Dynamics Over Time.

We explored the utility of brief Mycobacterium tuberculosis whole-genome sequencing (WGS) "snapshots" at a sentinel site within Lima, Peru, for evaluating local transmission dynamics over time. Within a 17-km2 area, 15 of 70 (21%) isolates with WGS collected during 2011-2012 and 22 of 81 (27%) collected during 2020-2021 were clustered (P = .414), and additional isolates clustered with those from outside the area.

Gut microbiome perturbation, antibiotic resistance, and Escherichia coli strain dynamics associated with international travel: a metagenomic analysis.

Background: Culture-based studies have shown that acquisition of extended-spectrum β-lactamase-producing Enterobacterales is common during international travel; however, little is known about the role of the gut microbiome before and during travel, nor about acquisition of other antimicrobial-resistant organisms. We aimed to identify (1) whether the gut microbiome provided colonisation resistance against antimicrobial-resistant organism acquisition, (2) the effect of travel and travel behaviours on the gut microbiome, and (3) the scale and global heterogeneity of antimicrobial-resistant organism acquisition.

Methods: In this metagenomic analysis, participants were recruited at three US travel clinics (Boston, MA; New York, NY; and Salt Lake City, UT) before international travel.

Clinical and Genomic Characterization of a Cohort of Patients With Klebsiella pneumoniae Bloodstream Infection.

Background: The clinical and microbial factors associated with Klebsiella pneumoniae bloodstream infections (BSIs) are not well characterized. Prior studies have focused on highly resistant or hypervirulent isolates, limiting our understanding of K. pneumoniae strains that commonly cause BSI.

Evaluating the relationship between community water and sanitation access and the global burden of antibiotic resistance: an ecological study.

Background: Antibiotic resistance is a leading cause of death, with the highest burden occurring in low-resource settings. There is little evidence on the potential for water, sanitation, and hygiene (WASH) access to reduce antibiotic resistance in humans. We aimed to determine the relationship between the burden of antibiotic resistance in humans and community access to drinking water and sanitation.

zol & fai: large-scale targeted detection and evolutionary investigation of gene clusters.

Many universally and conditionally important genes are genomically aggregated within clusters. Here, we introduce fai and zol, which together enable large-scale comparative analysis of different types of gene clusters and mobile-genetic elements (MGEs), such as biosynthetic gene clusters (BGCs) or viruses. Fundamentally, they overcome a current bottleneck to reliably perform comprehensive orthology inference at large scale across broad taxonomic contexts and thousands of genomes.

Global diversity of enterococci and description of 18 novel species.

Enterococci are commensal gut microbes of most land animals. They diversified over hundreds of millions of years adapting to evolving hosts and host diets. Of over 60 known enterococcal species, and uniquely emerged in the antibiotic era among leading causes of multidrug resistant hospital-associated infection.

SAP: Synteny-aware gene function prediction for bacteria using protein embeddings.

Motivation: Today, we know the function of only a small fraction of the protein sequences predicted from genomic data. This problem is even more salient for bacteria, which represent some of the most phylogenetically and metabolically diverse taxa on Earth. This low rate of bacterial gene annotation is compounded by the fact that most function prediction algorithms have focused on eukaryotes, and conventional annotation approaches rely on the presence of similar sequences in existing databases.

The Role of Mobile Genetic Elements in Virulence Factor Carriage from Symptomatic and Asymptomatic Cases of Escherichia coli Bacteriuria.

Uropathogenic Escherichia coli (UPEC) is extremely diverse genotypically and phenotypically. Individual strains can variably carry diverse virulence factors, making it challenging to define a molecular signature for this pathotype. For many bacterial pathogens, mobile genetic elements (MGEs) constitute a major mechanism of virulence factor acquisition.

Intrinsic Resistance to Colistin in the Genus .

A bacterial species is considered to be intrinsically resistant to an antimicrobial when nearly all of the wild-type isolates (i.e., those without acquired resistance) exhibit minimum inhibitory concentration (MIC) values that are sufficiently high such that susceptibility testing is unnecessary, and that the antimicrobial should not be considered for therapy.

Development of a prediction model for the acquisition of extended spectrum beta-lactam-resistant organisms in U.S. international travellers.

Background: Extended spectrum beta-lactamase producing Enterobacterales (ESBL-PE) present a risk to public health by limiting the efficacy of multiple classes of beta-lactam antibiotics against infection. International travellers may acquire these organisms and identifying individuals at high risk of acquisition could help inform clinical treatment or prevention strategies.

Methods: We used data collected from a cohort of 528 international travellers enrolled in a multicentre US-based study to derive a clinical prediction rule (CPR) to identify travellers who developed ESBL-PE colonization, defined as those with new ESBL positivity in stool upon return to the United States.