Shared mechanisms of enhanced plasmid maintenance and antibiotic tolerance mediated by the VapBC toxin:antitoxin system.

Unlabelled: Toxin:antitoxin (TA) systems are widespread in bacteria and were first identified as plasmid addiction systems that kill bacteria lacking a TA-encoding plasmid following cell division. TA systems have also been implicated in bacterial persistence and antibiotic tolerance, which can be precursors of antibiotic resistance. Here, we identified a clinical isolate of (CS14) with a remarkably stable pINV virulence plasmid; pINV is usually frequently lost from , but plasmid loss was not detected from CS14.

Tackling immunosuppression by Neisseria gonorrhoeae to facilitate vaccine design.

Gonorrhoea, caused by Neisseria gonorrhoeae, is a common sexually transmitted infection. Increasing multi-drug resistance and the impact of asymptomatic infections on sexual and reproductive health underline the need for an effective gonococcal vaccine. Outer membrane vesicles (OMVs) from Neisseria meningitidis induce modest cross-protection against gonococcal infection.

Gonococcal PorB: a multifaceted modulator of host immune responses.

Neisseria gonorrhoeae is a human-specific pathogen responsible for the sexually transmitted infection, gonorrhoea. N. gonorrhoeae promotes its survival by manipulating both innate and adaptive immune responses.

Evolution and exchange of plasmids in pathogenic .

Horizontal gene transfer (HGT) is a major influence in driving the spread of antimicrobial resistance (AMR) in many bacteria. A conjugative plasmid which is widespread in , pConj, prevented the use of tetracycline/doxycycline for treating gonococcal infection. Here, we show that pConj evolved in the related pathogen, , and has been acquired by the gonococcus from the meningococcus on multiple occasions.

There are three major β-lactamase plasmid variants which are associated with specific lineages and carry distinct TEM alleles.

is a significant threat to global health with an estimated incidence of over 80 million cases each year and high levels of antimicrobial resistance. The gonococcal β-lactamase plasmid, p, carries the TEM β-lactamase, which requires only one or two amino acid changes to become an extended-spectrum β-lactamase (ESBL); this would render last resort treatments for gonorrhoea ineffective. Although p is not mobile, it can be transferred by the conjugative plasmid, pConj, found in .

Evolution, persistence, and host adaption of a gonococcal AMR plasmid that emerged in the pre-antibiotic era.

Plasmids are diverse extrachromosomal elements significantly that contribute to interspecies dissemination of antimicrobial resistance (AMR) genes. However, within clinically important bacteria, plasmids can exhibit unexpected narrow host ranges, a phenomenon that has scarcely been examined. Here we show that pConj is largely restricted to the human-specific pathogen, Neisseria gonorrhoeae.

Meningococcal factor H-binding protein: implications for disease susceptibility, virulence, and vaccines.

Neisseria meningitidis is a human-adapted pathogen that causes meningitis and sepsis worldwide. N. meningitidis factor H-binding protein (fHbp) provides a mechanism for immune evasion by binding human complement factor H (CFH) to protect it from complement-mediated killing.

Pathogenic Bind the Complement Protein CFHR5 Outer Membrane Porins.

Neisseria meningitidis and Neisseria gonorrhoeae are important human pathogens that have evolved to bind the major negative regulator of the complement system, complement factor H (CFH). However, little is known about the interaction of pathogens with CFH-related proteins (CFHRs) which are structurally similar to CFH but lack the main complement regulatory domains found in CFH. Insights into the role of CFHRs have been hampered by a lack of specific reagents.

? Conflicts of Interest Between Species.

and are two obligate human pathogens that have evolved to be uniquely adapted to their host. The meningococcus is frequently carried asymptomatically in the nasopharynx, while gonococcal infection of the urogenital tract usually elicits a marked local inflammatory response. Other members of the genus are abundant in the upper airway where they could engage in co-operative or competitive interactions with both these pathogens.

Markerless gene editing in .

, the gonococcus, is a pathogen of major public health concern, but sophisticated approaches to gene manipulation are limited for this species. For example, there are few methods for generating markerless mutations, which allow the generation of precise point mutations and deletions without introducing additional DNA sequence. Markerless mutations are central to studying pathogenesis, the spread of antimicrobial resistance (AMR) and for vaccine development.

Virulence plasmid pINV as a genetic signature for phylogeny.

is a major health burden in low- and middle-income countries, where it is a leading cause of mortality associated with diarrhoea in children, and shows an increasing incidence among travellers and men having sex with men. Like all spp., has evolved from commensal following the acquisition of a large plasmid pINV, which contains genes essential for virulence.

Towards a better understanding of antimicrobial resistance dissemination: what can be learnt from studying model conjugative plasmids?

Bacteria can evolve rapidly by acquiring new traits such as virulence, metabolic properties, and most importantly, antimicrobial resistance, through horizontal gene transfer (HGT). Multidrug resistance in bacteria, especially in Gram-negative organisms, has become a global public health threat often through the spread of mobile genetic elements. Conjugation represents a major form of HGT and involves the transfer of DNA from a donor bacterium to a recipient by direct contact.

Maintenance of the Shigella sonnei Virulence Plasmid Is Dependent on Its Repertoire and Amino Acid Sequence of Toxin-Antitoxin Systems.

Shigella sonnei is a major cause of bacillary dysentery and an increasing concern due to the spread of multidrug resistance. S. sonnei harbors pINV, an ∼210 kb plasmid that encodes a type III secretion system (T3SS), which is essential for virulence.

Genome-wide association studies reveal the role of polymorphisms affecting factor H binding protein expression in host invasion by Neisseria meningitidis.

Many invasive bacterial diseases are caused by organisms that are ordinarily harmless components of the human microbiome. Effective interventions against these microbes require an understanding of the processes whereby symbiotic or commensal relationships transition into pathology. Here, we describe bacterial genome-wide association studies (GWAS) of Neisseria meningitidis, a common commensal of the human respiratory tract that is nevertheless a leading cause of meningitis and sepsis.

Evaluation of a Live Attenuated Vaccine Strain in the Human Enteroid Model.

is a leading cause of bacillary dysentery worldwide, responsible for high death rates especially among children under five in low-middle income countries. prevails in high-income countries and is becoming prevalent in industrializing countries, where multi-drug resistant strains have emerged, as a significant public health concern. One strategy to combat drug resistance in is the development of effective vaccines.

Methylation of PhoP by CheR Regulates Virulence.

The two-component system PhoP/PhoQ is essential for Salmonella enterica serovar Typhimurium virulence. Here, we report that PhoP is methylated extensively. Two consecutive glutamate (E) and aspartate (D)/E residues, i.

Bacterial rhomboid proteases mediate quality control of orphan membrane proteins.

Although multiprotein membrane complexes play crucial roles in bacterial physiology and virulence, the mechanisms governing their quality control remain incompletely understood. In particular, it is not known how unincorporated, orphan components of protein complexes are recognised and eliminated from membranes. Rhomboids, the most widespread and largest superfamily of intramembrane proteases, are known to play key roles in eukaryotes.

Commensal Neisseria cinerea impairs Neisseria meningitidis microcolony development and reduces pathogen colonisation of epithelial cells.

It is increasingly being recognised that the interplay between commensal and pathogenic bacteria can dictate the outcome of infection. Consequently, there is a need to understand how commensals interact with their human host and influence pathogen behaviour at epithelial surfaces. Neisseria meningitidis, a leading cause of sepsis and meningitis, exclusively colonises the human nasopharynx and shares this niche with several other Neisseria species, including the commensal Neisseria cinerea.

Neisseria gonorrhoeae Population Genomics: Use of the Gonococcal Core Genome to Improve Surveillance of Antimicrobial Resistance.

Background: Gonorrhea, caused by the bacterium Neisseria gonorrhoeae, is a globally prevalent sexually transmitted infection. The dynamics of gonococcal population biology have been poorly defined due to a lack of resolution in strain typing methods.

Methods: In this study, we assess how the core genome can be used to improve our understanding of gonococcal population structure compared with current typing schemes.

Association of Neisseria gonorrhoeae Plasmids With Distinct Lineages and The Economic Status of Their Country of Origin.

Plasmids are vehicles for horizontal gene transfer between bacteria, and in Neisseria gonorrhoeae plasmids can mediate high-level antimicrobial resistance (AMR). Using genomic and phylogenetic analyses, we show that plasmids are widespread in a collection of 3724 gonococcal isolates from 56 countries, and characterized the conjugative, β-lactamase and cryptic plasmids. We found that variants of the conjugative plasmid (which can mediate tetracycline resistance) and the β-lactamase plasmid expressing TEM-135 are associated with distinct gonococcal lineages.

DNA ADP-Ribosylation Stalls Replication and Is Reversed by RecF-Mediated Homologous Recombination and Nucleotide Excision Repair.

ADP-ribosylation of proteins is crucial for fundamental cellular processes. Despite increasing examples of DNA ADP-ribosylation, the impact of this modification on DNA metabolism and cell physiology is unknown. Here, we show that the DarTG toxin-antitoxin system from enteropathogenic Escherichia coli (EPEC) catalyzes reversible ADP-ribosylation of single-stranded DNA (ssDNA).

Contribution of σ and σ Factors to Expression of Class II in Neisseria meningitidis.

expresses multicomponent organelles called type four pili (Tfp), which are key virulence factors required for attachment to human cells during carriage and disease. Pilin (PilE) is the main component of Tfp, and isolates either have a class I locus and express pilins that undergo antigenic variation or have a class II locus and express invariant pilins. The transcriptional regulation of class I has been studied in both and , while the control of expression of class II has been elucidated in the nonpathogenic species However, the factors that govern the regulation of the class II gene in are not known.

Shigella host: Pathogen interactions: Keeping bacteria in the loop.

Shigella spp. are Gram-negative enteric pathogens and the leading cause of bacterial dysentery worldwide. Since the discovery more than three decades ago that the large virulence plasmid of Shigella is essential for pathogenesis, our understanding of how the bacterium orchestrates inflammation and tissue destruction at the mucosal surface has been informed by studies employing the rabbit ileal loop model.

An Overview of Neisseria meningitidis.

Neisseria meningitidis (the meningococcus) is a member of the normal nasopharyngeal microbiome in healthy individuals, but can cause septicemia and meningitis in susceptible individuals. In this chapter we provide an overview of the disease caused by N. meningitidis and the schemes used to type the meningococcus.