The premise of this specialty section is to present our readership with articles of the highest quality on the interconnected themes of bacterial pathogenesis and virulence, immunity to infection and vaccines. Our ethos is succinctly expressed in the Specialty Grand Challenge overview that opens this section (Christodoulides, 2022). The Research Topic features a broad diversity of articles from members of the editorial board, with a focus on important Gram-positive and Gram-negative bacterial pathogens causing human disease, namely Legionella pneumophila, Burkholderia pseudomallei, Staphylococcus spp., Yersinia pestis, Pseudomonas aeruginosa and Neisseria gonorrhoeae.

P. aeruginosa is a metabolically flexible Gram-negative organism that is a major opportunistic pathogen causing nosocomial infections (Dolan, 2020), and because of increased carbapenem resistance globally, it is ranked as a ‘high priority’ organism by the World Health Organisation for the development and introduction or new antibacterials and vaccines (World Health Orgainisation, 2024). P. aeruginosa is a formidable bacterium that can express a plethora of virulence factors, Type-secretion systems, quorum-sensing pathways and exopolysaccharides, and core resistance mechanisms such as drug permeability barriers, a chromosomally encoded AmpC enzyme and six superfamilies of multidrug efflux pumps (Miller and Arias, 2024). Efflux pumps play a major role in the pathogenesis of P. aeruginosa infection and resistance to treatment and clearance. In their mini-review, Fernandes and Jorth discuss the controversial and opposing roles of P. aeruginosa efflux pumps in virulence regulation. Efflux pumps function principally to eject antibiotics from the bacterial cell, although evidence is presented that these pumps may have alternative functions that can influence the virulence of P. aeruginosa. Efflux pumps are recognised targets for therapeutic interventions (Fernandes and Jorth) and they are potential antigens for vaccine development (Silva et al., 2024). The authors conclude that there may be unexpected consequences to targeting efflux pumps in the context of antimicrobial resistance and bacterial pathogenesis that must be considered when developing therapies.

Vaccine research was represented by papers on the Gram-negative bacteria Yersinia pestis and Neisseria gonorrhoeae. Y. pestis is a bacterium that has literally plagued humanity throughout our recorded history. It is a significant risk to public health and a potential bioweapon, and outbreaks of the plague are still reported today, but certainly not at pandemic levels. Y. pestis vaccines have consisted of killed whole cells, but these lack efficacy and provide only short-term protection against bubonic plague (Wang et al., 2013). Various strategies have been used to develop alternative vaccines, and Biryukov et al. described a live attenuated vaccine (LAV) derived from Y. pestis CO92 or C12 strains with a deletion of a type 3 secretion-associated gene (ΔyscN) or the pgm pigmentation locus, and cured of the pPst (PCP1) plasmid (CO92 pgm− pPst−). The authors evaluated the LAVs alone or combined with a dose of a protein subunit vaccine (rF1V or rV) in a mouse model of vaccination and challenge with aerosol (pneumonic) or subcutaneous (bubonic) virulent Y. pestis. The study was important in showing that lethal infection with virulent, nonencapsulated Y. pestis could be prevented with flexible vaccination strategies using i) LAV and rF1V or rV protein subunit vaccine, and ii) vaccines with post-exposure streptomycin antibiotic treatment.

Infection with the obligate human pathogen N. gonorrhoeae causes the sexually transmitted disease gonorrhoea, and like P. aeruginosa, the gonococcus rests within the WHO ‘high priority’ list of pathogens, with antimicrobial resistance increasing globally. No vaccine exists to prevent gonorrhoea (Wetzler et al., 2016), and in recent years, research has focused on identifying putative vaccine candidates from microbiological–biochemical studies of the gonococcus and using technologies that exploit whole genome(s) information, e.g., proteomics, bioinformatics, and transcriptomics. The study from Dijokaite-Guraliuc et al. used an immuno-proteomics approach to examine the reactivity of a gonococcal proteome with sera from patients with uncomplicated gonorrhoea. Using a bio-informatics approach, the authors defined a final collection of 33 proteins that contained 24 OMPs/extracellular proteins never previously studied as vaccine antigens, 6 proteins with homologs in Neisseria meningitidis previously reported to generate functional immune responses, and 3 unknown proteins. The study is important in not only confirming the presence of candidate vaccine antigens reported using other ‘omic’ platforms, but also in presenting new antigens for further vaccine development.

The final collection of Research Topic papers detail certain aspects of the pathogenesis of Burkholderia pseudomallei, Staphylococcus epidermidis and Legionella pneumophila. B. pseudomallei is an environmental bacterium and causes melioidosis (Meumann et al., 2024), a complex, often fatal disease manifested by acute pneumonia, bacteraemia-sepsis and localised infection. In addition, patients can present with a chronic infection or a subclinical infection. The pathogen is also of concern as a potential Category B bioweapon (Rathjen and Shahbodaghi, 2021). The BALB/c mouse is useful for studying the pathogenesis of acute melioidosis and Klimko et al showed that low levels of transmission of B. pseudomallei were possible from clinically infected mice to naïve mice housed in the same cage(s). S. epidermidis is a common cause of biofilm formation and infection in cerebrospinal fluid shunt catheters inserted in infants with hydrocephalus (Simon et al., 2014). Adult mouse models are available that mimic S. epidermidis and S. aureus CNS catheter infections, and the study from Skar et al. described how a newly adapted infant mouse model of CNS catheter infection helped to identify key factors in the host immune response to staphylococcal infections in the CNS. In the infant mouse, S. epidermidis showed higher parenchymal spread and the absence of the elevated pro-inflammatory cytokines as seen in infected adult mice. Notably, an attenuated inflammatory response may contribute to the increased infection risk observed in neonates. L. pneumophila is an accidental pathogen that causes Legionnaire’s disease (Fraser et al., 1977), which is a severe atypical pneumonia resulting from bacterial replication within lung alveolar macrophages. During its intracellular lifecycle, this bacterium establishes an endoplasmic reticulum-derived organelle within which it replicates. In the article from Wilkins et al. the authors examined the role of esterified fatty acids in bacterial replication in macrophages and concluded that intracellular replication of L. pneumophila was a function of lipid bilayer disorder and hydrophobic thickness. The final paper in our showcase from Reed et al. assessed the potentially different antibacterial properties of eumelanin-inspired derivatives and showed that a hydrophobic derivative EIPE-1 inhibited Gram-positive bacteria in a cytoplasmic membrane-directed manner, independent of oxygen.

In conclusion, the variety of articles included in the Research Topic merely touch on the breadth of research in bacterial pathogenesis, vaccines and immunity to bacterial infections, and we welcome submissions that increase our basic understanding of all three.