The role of the L421P mutation in Penicillin-Binding Protein 1 (PBP1) in the evolution of chromosomally mediated penicillin resistance in .

Unlabelled: encodes a mutated variant of penicillin-binding protein 1 (PBP1) and is a key resistance determinant that increases the penicillin MIC (MIC ) above the clinical breakpoint in . Despite the removal of penicillin from treatment guidelines for gonococcal infections in the 1980s, is present in nearly 50% of current isolates in the PubMLST database. Bioinformatic analysis indicates that is exclusive to isolates, whereas Leu-421 is 100% conserved in other species.

Quantifying the impact of antibiotic use and genetic determinants of resistance on bacterial lineage dynamics.

The dynamics of antimicrobial resistance in bacterial populations are informed by the fitness impact of genetic determinants of resistance and antibiotic pressure. However, estimates of real-world fitness impact have been lacking. To address this gap, we developed a hierarchical Bayesian phylodynamic model to quantify contributions of resistance determinants to strain success in a 20-year collection of isolates.

Complete genome sequences of associated with mortality events in avian species.

is a potential bacterial pathogen that affects chickens. We present 22 complete genome sequences of clinical isolates to facilitate the genomic analysis and the development of diagnostic tools.

mSphere of Influence: Predicting the evolution of pathogen populations.

Tatum D. Mortimer works in the field of pathogen population genomics and evolution. In this mSphere of Influence article, she reflects on how "Frequency-dependent selection can forecast evolution in " by Azarian et al.

A Genomic Perspective on the Near-term Impact of Doxycycline Post-exposure Prophylaxis on Neisseria gonorrhoeae Antimicrobial Resistance.

Pre-existing tetracycline resistance in Neisseria gonorrhoeae limits the effectiveness of post-exposure prophylaxis (PEP) with doxycycline against gonorrhea, and selection for tetracycline resistance may influence prevalence of multi-drug resistant strains. Using genomic and antimicrobial susceptibility data from N. gonorrhoeae, we assessed the near-term impact of doxycycline PEP on N.

A genomic perspective on the near-term impact of doxycycline post-exposure prophylaxis on antimicrobial resistance.

Post-exposure prophylaxis with doxycycline (doxyPEP) is being introduced to prevent bacterial sexually transmitted infections (STIs). Pre-existing tetracycline resistance in limits doxyPEP effectiveness against gonorrhea, and selection for tetracycline resistant lineages may influence prevalence of resistance to other antimicrobials via selection for multi-drug resistant strains. Using genomic and antimicrobial susceptibility data from 5,644 clinical isolates of , we assessed the near-term impact of doxyPEP on antimicrobial resistance.

Neisseria gonorrhoeae diagnostic escape from a gyrA-based test for ciprofloxacin susceptibility and the effect on zoliflodacin resistance: a bacterial genetics and experimental evolution study.

Background: The aetiological bacterial agent of gonorrhoea, Neisseria gonorrhoeae, has become resistant to each of the first-line antibiotics used to treat it, including ciprofloxacin. One diagnostic approach to identify ciprofloxacin-susceptible isolates is to determine codon 91 in the gene encoding the A subunit of DNA gyrase, gyrA, where coding for the wild-type serine (gyrA) is associated with ciprofloxacin susceptibility and phenylalanine (gyrA) with resistance. The aim of this study was to investigate the possibility of diagnostic escape from gyrA susceptibility testing.

Machine learning models for Neisseria gonorrhoeae antimicrobial susceptibility tests.

Neisseria gonorrhoeae is an urgent public health threat due to the emergence of antibiotic resistance. As most isolates in the United States are susceptible to at least one antibiotic, rapid molecular antimicrobial susceptibility tests (ASTs) would offer the opportunity to tailor antibiotic therapy, thereby expanding treatment options. With genome sequence and antibiotic resistance phenotype data for nearly 20,000 clinical N.

Rapid adaptation of a complex trait during experimental evolution of .

Tuberculosis (TB), caused by (), is a leading cause of death due to infectious disease. TB is not traditionally associated with biofilms, but biofilms are linked with drug and immune tolerance and there is increasing recognition of their contribution to the recalcitrance of TB infections. Here, we used experimental evolution to investigate this complex phenotype and identify candidate loci controlling biofilm formation.

Loci for prediction of penicillin and tetracycline susceptibility in Neisseria gonorrhoeae: a genome-wide association study.

Background: Neisseria gonorrhoeae poses an urgent public health threat because of increasing antimicrobial resistance; however, much of the circulating population remains susceptible to historical treatment regimens. Point-of-care diagnostics that report susceptibility could allow for reintroduction of these regimens, but development of such diagnostics has been restricted to ciprofloxacin, for which susceptibility can be predicted from a single locus. We aimed to define genetic variants associated with susceptibility to penicillin and tetracycline.

Sculpting the Bacterial -Glycoproteome: Functional Analyses of Orthologous Oligosaccharyltransferases with Diverse Targeting Specificities.

Protein glycosylation systems are widely recognized in bacteria, including members of the genus . In most bacterial species, the molecular mechanisms and evolutionary contexts underpinning target protein selection and the glycan repertoire remain poorly understood. Broad-spectrum -linked protein glycosylation occurs in all human-associated species groups within the genus , but knowledge of their individual glycoprotein repertoires is limited.

Interactions between Loci Contributing to Antimicrobial Resistance and Virulence in Neisseria gonorrhoeae.

In a recent mBio article, Ayala et al. (mBio 13:e00276-22, 2022, https://doi.org/10.

A community-driven resource for genomic epidemiology and antimicrobial resistance prediction of Neisseria gonorrhoeae at Pathogenwatch.

Background: Antimicrobial-resistant (AMR) Neisseria gonorrhoeae is an urgent threat to public health, as strains resistant to at least one of the two last-line antibiotics used in empiric therapy of gonorrhoea, ceftriaxone and azithromycin, have spread internationally. Whole genome sequencing (WGS) data can be used to identify new AMR clones and transmission networks and inform the development of point-of-care tests for antimicrobial susceptibility, novel antimicrobials and vaccines. Community-driven tools that provide an easy access to and analysis of genomic and epidemiological data is the way forward for public health surveillance.

Emergence and evolution of antimicrobial resistance genes and mutations in Neisseria gonorrhoeae.

Background: Antimicrobial resistance in Neisseria gonorrhoeae is a global health concern. Strains from two internationally circulating sequence types, ST-7363 and ST-1901, have acquired resistance to third-generation cephalosporins, mainly due to mosaic penA alleles. These two STs were first detected in Japan; however, the timeline, mechanism, and process of emergence and spread of these mosaic penA alleles to other countries remain unknown.

Draft Genome Sequences of Three Penicillin-Resistant Neisseria gonorrhoeae Strains Isolated in Cincinnati, Ohio, in 1994.

Here, we report the draft genome sequences of three penicillin-resistant isolates. We include associated data on MICs and genetic relationships to other strains collected from across the United States. Resistance mutations known to contribute to reduced penicillin susceptibility are annotated in each genome.

Using rapid point-of-care tests to inform antibiotic choice to mitigate drug resistance in gonorrhoea.

BackgroundThe first cases of extensively drug resistant gonorrhoea were recorded in the United Kingdom in 2018. There is a public health need for strategies on how to deploy existing and novel antibiotics to minimise the risk of resistance development. As rapid point-of-care tests (POCTs) to predict susceptibility are coming to clinical use, coupling the introduction of an antibiotic with diagnostics that can slow resistance emergence may offer a novel paradigm for maximising antibiotic benefits.

Increased power from conditional bacterial genome-wide association identifies macrolide resistance mutations in Neisseria gonorrhoeae.

The emergence of resistance to azithromycin complicates treatment of Neisseria gonorrhoeae, the etiologic agent of gonorrhea. Substantial azithromycin resistance remains unexplained after accounting for known resistance mutations. Bacterial genome-wide association studies (GWAS) can identify novel resistance genes but must control for genetic confounders while maintaining power.

The Distribution and Spread of Susceptible and Resistant Neisseria gonorrhoeae Across Demographic Groups in a Major Metropolitan Center.

Background: Genomic epidemiology studies of gonorrhea in the United States have primarily focused on national surveillance for antibiotic resistance, and patterns of local transmission between demographic groups of resistant and susceptible strains are unknown.

Methods: We analyzed a convenience sample of genome sequences, antibiotic susceptibility, and patient data from 897 gonococcal isolates cultured at the New York City (NYC) Public Health Laboratory from NYC Department of Health and Mental Hygiene (DOHMH) Sexual Health Clinic (SHC) patients, primarily in 2012-2013. We reconstructed the gonococcal phylogeny, defined transmission clusters using a 10 nonrecombinant single nucleotide polymorphism threshold, tested for clustering of demographic groups, and placed NYC isolates in a global phylogenetic context.

Adaptation to the cervical environment is associated with increased antibiotic susceptibility in Neisseria gonorrhoeae.

Neisseria gonorrhoeae is an urgent public health threat due to rapidly increasing incidence and antibiotic resistance. In contrast with the trend of increasing resistance, clinical isolates that have reverted to susceptibility regularly appear, prompting questions about which pressures compete with antibiotics to shape gonococcal evolution. Here, we used genome-wide association to identify loss-of-function (LOF) mutations in the efflux pump mtrCDE operon as a mechanism of increased antibiotic susceptibility and demonstrate that these mutations are overrepresented in cervical relative to urethral isolates.

Lateral Gene Transfer Shapes Diversity of spp.

spp. are pathognomonic for bacterial vaginosis, which increases the risk of preterm birth and the transmission of sexually transmitted infections. spp.