Obstetric and Neonatal Invasive Meningococcal Disease Caused by Neisseria meningitidis Serogroup W, Western Australia, Australia.

Three mother-baby pairs with invasive meningococcal disease occurred over 7 months in Western Australia, Australia, at a time when serogroup W sequence type 11 clonal complex was the predominant local strain. One mother and 2 neonates died, highlighting the role of this strain as a cause of obstetric and early neonatal death.

Microevolution and Its Impact on Hypervirulence, Antimicrobial Resistance, and Vaccine Escape in .

is commensal of the human pharynx and occasionally invades the host, causing the life-threatening illness invasive meningococcal disease. The meningococcus is a highly diverse and adaptable organism thanks to natural competence, a propensity for recombination, and a highly repetitive genome. These mechanisms together result in a high level of antigenic variation to invade diverse human hosts and evade their innate and adaptive immune responses.

Phosphoethanolamine Transferases as Drug Discovery Targets for Therapeutic Treatment of Multi-Drug Resistant Pathogenic Gram-Negative Bacteria.

Antibiotic resistance caused by multidrug-resistant (MDR) bacteria is a major challenge to global public health. Polymyxins are increasingly being used as last-in-line antibiotics to treat MDR Gram-negative bacterial infections, but resistance development renders them ineffective for empirical therapy. The main mechanism that bacteria use to defend against polymyxins is to modify the lipid A headgroups of the outer membrane by adding phosphoethanolamine (PEA) moieties.

Travel-associated lineages and unique endemic antimicrobial-susceptible lineages of predominate in Western Australia.

In Australia, gonococcal isolates are monitored for antimicrobial susceptibilities. In Western Australia (WA), gonorrhoea notification rates increased by 63 % between 2013 and 2016, with the steepest increase occurring between 2015 and 2016, before stabilizing at this higher baseline between 2017 and 2020. This increased prevalence was associated with antimicrobial-susceptible (AMS) lineages.

Novel small molecules that increase the susceptibility of Neisseria gonorrhoeae to cationic antimicrobial peptides by inhibiting lipid A phosphoethanolamine transferase.

Objectives: Neisseria gonorrhoeae is an exclusively human pathogen that commonly infects the urogenital tract resulting in gonorrhoea. Empirical treatment of gonorrhoea with antibiotics has led to multidrug resistance and the need for new therapeutics. Inactivation of lipooligosaccharide phosphoethanolamine transferase A (EptA), which attaches phosphoethanolamine to lipid A, results in attenuation of the pathogen in infection models.

The Host-Pathogen Interactions and Epicellular Lifestyle of .

is a gram-negative diplococcus and a transient commensal of the human nasopharynx. It shares and competes for this niche with a number of other species including and . Unlike these other members of the genus, may become invasive, crossing the epithelium of the nasopharynx and entering the bloodstream, where it rapidly proliferates causing a syndrome known as Invasive Meningococcal Disease (IMD).

Broad-spectrum in vitro activity of macrophage infectivity potentiator inhibitors against Gram-negative bacteria and Leishmania major.

Background: The macrophage infectivity potentiator (Mip) protein, which belongs to the immunophilin superfamily, is a peptidyl-prolyl cis/trans isomerase (PPIase) enzyme. Mip has been shown to be important for virulence in a wide range of pathogenic microorganisms. It has previously been demonstrated that small-molecule compounds designed to target Mip from the Gram-negative bacterium Burkholderia pseudomallei bind at the site of enzymatic activity of the protein, inhibiting the in vitro activity of Mip.

Modelling evolutionary pathways for commensalism and hypervirulence in .

, the meningococcus resides exclusively in humans and causes invasive meningococcal disease (IMD). The population of is structured into stable clonal complexes by limited horizontal recombination in this naturally transformable species. is an opportunistic pathogen, with some clonal complexes, such as cc53, effectively acting as commensal colonizers, while other genetic lineages, such as cc11, are rarely colonizers but are over-represented in IMD and are termed hypervirulent.

Conformational flexibility of EptA driven by an interdomain helix provides insights for enzyme-substrate recognition.

Many pathogenic gram-negative bacteria have developed mechanisms to increase resistance to cationic antimicrobial peptides by modifying the lipid A moiety. One modification is the addition of phospho-ethano-lamine to lipid A by the enzyme phospho-ethano-lamine transferase (EptA). Previously we reported the structure of EptA from , revealing a two-domain architecture consisting of a periplasmic facing soluble domain and a transmembrane domain, linked together by a bridging helix.

B Part of It School Leaver Study: A Repeat Cross-Sectional Study to Assess the Impact of Increasing Coverage With Meningococcal B (4CMenB) Vaccine on Carriage of Neisseria meningitidis.

Background: Recombinant protein-based vaccines targeting serogroup B meningococci protect against invasive disease but impacts on carriage are uncertain. This study assessed carriage prevalence of disease-associated meningococci in 2018-2020 as the proportion of vaccinated adolescents increased following introduction of a school-based 4CMenB immunization program.

Methods: Eligible participants who completed high school (aged 17-25) in South Australia in the previous year had an oropharyngeal swab taken and completed a risk factor questionnaire.

Vaccine Candidates for the Control and Prevention of the Sexually Transmitted Disease Gonorrhea.

The World Health Organization (WHO) has placed on the global priority list of antimicrobial resistant pathogens and is urgently seeking the development of new intervention strategies. causes 86.9 million cases globally per annum.

Anti-Virulence Therapeutic Approaches for .

While antimicrobial resistance (AMR) is seen in both and , the former has become resistant to commonly available over-the-counter antibiotic treatments. It is imperative then to develop new therapies that combat current AMR isolates whilst also circumventing the pathways leading to the development of AMR. This review highlights the growing research interest in developing anti-virulence therapies (AVTs) which are directed towards inhibiting virulence factors to prevent infection.

Meningococcal Disease-Associated Prophage-Like Elements Are Present in Neisseria gonorrhoeae and Some Commensal Neisseria Species.

Neisseria spp. possess four genogroups of filamentous prophages, termed Nf1 to 4. A filamentous bacteriophage from the Nf1 genogroup termed meningococcal disease-associated phage (MDA φ) is associated with clonal complexes of Neisseria meningitidis that cause invasive meningococcal disease.

Meningococcal B Vaccine and Meningococcal Carriage in Adolescents in Australia.

Background: The meningococcal group B vaccine 4CMenB is a new, recombinant protein-based vaccine that is licensed to protect against invasive group B meningococcal disease. However, its role in preventing transmission and, therefore, inducing population (herd) protection is uncertain.

Methods: We used cluster randomization to assign, according to school, students in years 10 to 12 (age, 15 to 18 years) in South Australia to receive 4CMenB vaccination either at baseline (intervention) or at 12 months (control).

Genomic characterisation of perinatal Western Australian Streptococcus agalactiae isolates.

As a leading cause of neonatal sepsis, Streptococcus agalactiae, commonly known as Group B Streptococcus, is a major neonatal pathogen. Current global screening practices employ risk- or culture-based protocols for detection of these organisms. In Western Australia (WA), universal culture-based screening is provided, with subsequent intrapartum antibiotic prophylaxis for all S.

Peptidyl-Prolyl Isomerase Is Essential for Proteome Homeostasis and Virulence in Burkholderia pseudomallei.

is the causative agent of melioidosis, a disease endemic to Southeast Asia and northern Australia. Mortality rates in these areas are high even with antimicrobial treatment, and there are few options for effective therapy. Therefore, there is a need to identify antibacterial targets for the development of novel treatments.

The Detroit 562 Pharyngeal Immortalized Cell Line Model for the Assessment of Infectivity of Pathogenic Neisseria sp.

Neisseria meningitidis and Neisseria gonorrhoeae are obligate pathogens of the human host. Due to their adaptation to the human host, many factors required for infection are specialized for the human host to the point that natural infection processes are difficult to replicate in animal models. Immortalized human cell lines have been used to identify the host factors necessary for successful colonization of human mucosal surfaces.

Enzyme targets for drug design of new anti-virulence therapeutics.

Society has benefitted greatly from the use of antibiotics. Unfortunately, the misuse of these valuable molecules has resulted in increased levels of antibiotic resistance, a major global and public health issue. This resistance and the reliance on a small number of biological targets for the development of antibiotics emphasizes the need for new targets.

Structure-Function Relationships of the Neisserial EptA Enzyme Responsible for Phosphoethanolamine Decoration of Lipid A: Rationale for Drug Targeting.

Bacteria cause disease by two general mechanisms: the action of their toxins on host cells and induction of a pro-inflammatory response that can lead to a deleterious cytokine/chemokine response (e.g., the so-called cytokine storm) often seen in bacteremia/septicemia.

Structural and biochemical insights into the disulfide reductase mechanism of DsbD, an essential enzyme for neisserial pathogens.

The worldwide incidence of neisserial infections, particularly gonococcal infections, is increasingly associated with antibiotic-resistant strains. In particular, extensively drug-resistant strains that are resistant to third-generation cephalosporins are a major public health concern. There is a pressing clinical need to identify new targets for the development of antibiotics effective against -specific processes.

B Part of It protocol: a cluster randomised controlled trial to assess the impact of 4CMenB vaccine on pharyngeal carriage of in adolescents.

Introduction: South Australia (SA) has the highest notification rate of invasive meningococcal disease in Australia with the majority of cases due to serogroup B. is carried in the pharynx, with adolescents having the highest rates of carriage. A vaccine designed to offer protection against serogroup B (4CMenB) is licensed in Australia.

Communication Ambassadors-an Australian Social Media Initiative to Develop Communication Skills in Early Career Scientists.

Science communication is a skill set to be developed through ongoing interactions with different stakeholders across a variety of platforms. Opportunities to engage the general public are typically reserved for senior scientists, but the use of social media in science communication allows all scientists to instantaneously disseminate their findings and interact with online users. The Communication Ambassador program is a social media initiative launched by the Australian Society for Microbiology to expand the online presence and science communication portfolios of early-career scientists.