Review

Authors: Sarah Jane Quillin, H Steven Seifert

The host-adapted human pathogen Neisseria gonorrhoeae is the causative agent of gonorrhoea. Consistent with its proposed evolution from an ancestral commensal bacterium, N. gonorrhoeae has retained features that are common in commensals, but it has also developed unique features that are crucial to its pathogenesis. The continued worldwide incidence of gonorrhoeal infection, coupled with the rising resistance to antimicrobials and the difficulties in controlling the disease in developing countries, highlights the need to better understand the molecular basis of N. gonorrhoeae infection. This knowledge will facilitate disease prevention, surveillance and control, improve diagnostics and may help to facilitate the development of effective vaccines or new therapeutics. In this Review, we discuss sex-related symptomatic gonorrhoeal disease and provide an overview of the bacterial factors that are important for the different stages of pathogenesis, including transmission, colonization and immune evasion, and we discuss the problem of antibiotic resistance.

Topics: Adaptation, Physiological; Anti-Bacterial Agents; Drug Resistance, Bacterial; Gonorrhea; Humans; Neisseria gonorrhoeae

PubMed: 29430011
DOI: 10.1038/nrmicro.2017.169

Review

Authors: Nadine G Rouphael, David S Stephens

Neisseria meningitidis (the meningococcus) causes significant morbidity and mortality in children and young adults worldwide through epidemic or sporadic meningitis and/or septicemia. In this review, we describe the biology, microbiology, and epidemiology of this exclusive human pathogen. N.meningitidis is a fastidious, encapsulated, aerobic gram-negative diplococcus. Colonies are positive by the oxidase test and most strains utilize maltose. The phenotypic classification of meningococci, based on structural differences in capsular polysaccharide, lipooligosaccharide (LOS) and outer membrane proteins, is now complemented by genome sequence typing (ST). The epidemiological profile of N. meningitidis is variable in different populations and over time and virulence of the meningococcus is based on a transformable/plastic genome and expression of certain capsular polysaccharides (serogroups A, B, C, W-135, Y and X) and non-capsular antigens. N. meningitidis colonizes mucosal surfaces using a multifactorial process involving pili, twitching motility, LOS, opacity associated, and other surface proteins. Certain clonal groups have an increased capacity to gain access to the blood, evade innate immune responses, multiply, and cause systemic disease. Although new vaccines hold great promise, meningococcal infection continues to be reported in both developed and developing countries, where universal vaccine coverage is absent and antibiotic resistance increasingly more common.

Topics: Age Factors; Animals; Bacterial Capsules; Geography; Humans; Meningitis, Meningococcal; Models, Biological; Neisseria meningitidis; Phenotype; Virulence

PubMed: 21993636
DOI: 10.1007/978-1-61779-346-2_1

Authors: Jesús Arenas

Topics: Neisseria; Virulence; Neisseria gonorrhoeae; Neisseria meningitidis; Vaccines; Drug Resistance, Microbial

PubMed: 36683679
DOI: 10.3389/fcimb.2022.1119244

Authors: Mary C Gray, Keena S Thomas, Evan R Lamb...

The bacterial pathogen is an urgent global health problem due to increasing numbers of infections, coupled with rampant antibiotic resistance. Vaccines against gonorrhea are being prioritized to combat drug-resistant . Meningococcal serogroup B vaccines such as four-component meningococcal B vaccine (4CMenB) are predicted by epidemiology studies to cross-protect individuals from natural infection with and elicit antibodies that cross-react with . Evaluation of vaccine candidates for gonorrhea requires a suite of assays for predicting efficacy and in animal models of infection, including the role of antibodies elicited by immunization. Here, we present the development and optimization of assays to evaluate antibody functionality after immunization of mice: antibody binding to intact , serum bactericidal activity, and opsonophagocytic killing activity using primary human neutrophils [polymorphonuclear leukocytes (PMNs)]. These assays were developed with purified antibodies against and used to evaluate serum from mice that were vaccinated with 4CMenB or given alum as a negative control. Results from these assays will help prioritize gonorrhea vaccine candidates for advanced preclinical to early clinical studies and will contribute to identifying correlates and mechanisms of immune protection against .

Topics: Humans; Mice; Animals; Meningococcal Vaccines; Neisseria gonorrhoeae; Gonorrhea; Meningococcal Infections; Neisseria meningitidis; Bacterial Vaccines; Antibodies; Vaccines, Combined; Antibodies, Bacterial; Neisseria meningitidis, Serogroup B; Antigens, Bacterial

PubMed: 37991382
DOI: 10.1128/iai.00309-23

Review

Authors: Jose A Bazan, David S Stephens, Abigail Norris Turner...

PURPOSE OF REVIEW

Neisseria meningitidis (Nm) is primarily associated with asymptomatic nasopharyngeal carriage and invasive meningococcal disease (sepsis and meningitis), but like N. gonorrhoea (Ng), Nm can colonize urogenital and rectal mucosal surfaces and cause disease. First noted in 2015, but with origins in 2011, male urethritis clusters caused by a novel Nm clade were reported in the USA (the US_NmUC). This review describes research developments that characterize this urogenital-tropic Nm.

RECENT FINDINGS

The US_NmUC evolved from encapsulated Nm serogroup C strains. Loss of capsule expression, lipooligosaccharide (LOS) sialylation, genetic acquisition of gonococcal alleles (including the gonococcal anaerobic growth aniA/norB cassette), antimicrobial peptide heteroresistance and high surface expression of a unique factor-H-binding protein, can contribute to the urethra-tropic phenotype. Loss-of-function mutations in mtrC are overrepresented in clade isolates. Similar to Ng, repeat US_NmUC urethritis episodes can occur. The US_NmUC is now circulating in the UK and Southeast Asia. Genomic sequencing has defined the clade and rapid diagnostic tests are being developed for surveillance.

SUMMARY

The US_NmUC emerged as a cause of urethritis due to acquisition of gonococcal genetic determinants and phenotypic traits that facilitate urogenital tract infection. The epidemiology and pathogenesis of this urogenital-tropic pathogen continues to be defined.

Topics: Communicable Diseases, Emerging; Humans; Meningococcal Infections; Neisseria meningitidis; Urethritis

PubMed: 33278178
DOI: 10.1097/QCO.0000000000000697

Authors: Dona Benadof

Topics: Humans; Neisseria sicca; Neisseriaceae Infections

PubMed: 19915756
DOI: No ID Found

Review

Authors: Pablo Yagupsky

Kingella kingae is a common etiology of pediatric bacteremia and the leading agent of osteomyelitis and septic arthritis in children aged 6 to 36 months. This Gram-negative bacterium is carried asymptomatically in the oropharynx and disseminates by close interpersonal contact. The colonized epithelium is the source of bloodstream invasion and dissemination to distant sites, and certain clones show significant association with bacteremia, osteoarthritis, or endocarditis. Kingella kingae produces an RTX (repeat-in-toxin) toxin with broad-spectrum cytotoxicity that probably facilitates mucosal colonization and persistence of the organism in the bloodstream and deep body tissues. With the exception of patients with endocardial involvement, children with K. kingae diseases often show only mild symptoms and signs, necessitating clinical acumen. The isolation of K. kingae on routine solid media is suboptimal, and detection of the bacterium is significantly improved by inoculating exudates into blood culture bottles and the use of PCR-based assays. The organism is generally susceptible to antibiotics that are administered to young patients with joint and bone infections. β-Lactamase production is clonal, and the local prevalence of β-lactamase-producing strains is variable. If adequately and promptly treated, invasive K. kingae infections with no endocardial involvement usually run a benign clinical course.

Topics: Anti-Bacterial Agents; Bacteremia; Genome, Bacterial; Humans; Kingella kingae; Neisseriaceae Infections; Virulence Factors

PubMed: 25567222
DOI: 10.1128/CMR.00028-14

Review

Authors: Bente Børud, Michael Koomey

The genus , which colonizes mucosal surfaces, includes both commensal and pathogenic species that are exclusive to humans. The two pathogenic species are closely related but cause quite different diseases, meningococcal sepsis and meningitis () and sexually transmitted gonorrhea ). Although obvious differences in bacterial niches and mechanisms for transmission exists, pathogenic have high levels of conservation at the levels of nucleotide sequences, gene content and synteny. Species of express broad-spectrum -linked protein glycosylation where the glycoproteins are largely transmembrane proteins or lipoproteins localized on the cell surface or in the periplasm. There are diverse functions among the identified glycoproteins, for example type IV biogenesis proteins, proteins involved in antimicrobial resistance, as well as surface proteins that have been suggested as vaccine candidates. The most abundant glycoprotein, PilE, is the major subunit of pili which are an important colonization factor. The glycans attached can vary extensively due to phase variation of protein glycosylation ( genes and polymorphic gene content. The exact roles of glycosylation in remains to be determined, but increasing evidence suggests that glycan variability can be a strategy to evade the human immune system. In addition, pathogenic and commensal appear to have significant glycosylation differences. Here, the current knowledge and implications of protein glycosylation genes, glycan diversity, glycoproteins and immunogenicity in pathogenic are summarized and discussed.

Topics: Humans; Bacterial Proteins; Glycoproteins; Glycosylation; Neisseria gonorrhoeae; Neisseria meningitidis; Polysaccharides; Meningitis, Meningococcal; Gonorrhea

PubMed: 38808060
DOI: 10.3389/fcimb.2024.1407863

Authors: Sammy Nyongesa, Philipp M Weber, Ève Bernet...

Rod-shaped bacteria typically elongate and divide by transverse fission. However, several bacterial species can form rod-shaped cells that divide longitudinally. Here, we study the evolution of cell shape and division mode within the family Neisseriaceae, which includes Gram-negative coccoid and rod-shaped species. In particular, bacteria of the genera Alysiella, Simonsiella and Conchiformibius, which can be found in the oral cavity of mammals, are multicellular and divide longitudinally. We use comparative genomics and ultrastructural microscopy to infer that longitudinal division within Neisseriaceae evolved from a rod-shaped ancestor. In multicellular longitudinally-dividing species, neighbouring cells within multicellular filaments are attached by their lateral peptidoglycan. In these bacteria, peptidoglycan insertion does not appear concentric, i.e. from the cell periphery to its centre, but as a medial sheet guillotining each cell. Finally, we identify genes and alleles associated with multicellularity and longitudinal division, including the acquisition of amidase-encoding gene amiC2, and amino acid changes in proteins including MreB and FtsA. Introduction of amiC2 and allelic substitution of mreB in a rod-shaped species that divides by transverse fission results in shorter cells with longer septa. Our work sheds light on the evolution of multicellularity and longitudinal division in bacteria, and suggests that members of the Neisseriaceae family may be good models to study these processes due to their morphological plasticity and genetic tractability.

Topics: Animals; Bacterial Proteins; Biological Evolution; Cell Division; Cell Wall; Mammals; Neisseriaceae; Peptidoglycan

PubMed: 35995772
DOI: 10.1038/s41467-022-32260-w

Review

Authors: Yan Zhang

Bacteria and archaea possess numerous defense systems to combat viral infections and other mobile genetic elements. Uniquely among these, CRISPR-Cas (clustered, regularly interspaced short palindromic repeats-CRISPR associated) provides adaptive genetic interference against foreign nucleic acids. Here we review recent advances on the CRISPR-Cas9 system in Neisseria spp, with a focus on its biological functions in genetic transfer, its mechanistic features that establish new paradigms and its technological applications in eukaryotic genome engineering.

Topics: CRISPR-Cas Systems; Gene Targeting; Neisseria

PubMed: 28369433
DOI: 10.1093/femspd/ftx036