Open research questions in Bacterial Infections and Vaccines

What the literature leaves open

• The study identifies a gap in the understanding of the clinical characteristics and hospitalization-related factors of pertussis in children aged 0-6 years. The gap is related to the waning vaccine-induced antibodies and the shift in the age distribution of pertussis cases.

  Analysis of Clinical Characteristics of Pertussis in Children Aged 0–6 Years in Tertiary and Pediatric Hospitals of Jiangsu Province from January to May 2024 · 2026 · DOI

• How this unusually large non-pilin protein is stably displayed at the pilus tip, and why is it required for pilus biogenesis, remains unknown.

  A short C-terminal plug motif in a conserved type 4 pilus component controls pilus-tip localisation and filament biogenesis · 2026 · DOI

• Whilst many studies have examined the relationship between bacterial meningitis outbreaks and climate across Africa, this has rarely been examined on a continental level.

  Spatiotemporal Modelling of Bacterial Meningitis Outbreaks using Climatic Drivers in Africa · 2026 · DOI

• IMPORTANCE Comparing genomes from different clinical isolates of the same pathogenic bacterial species has identified genes associated with virulence, but many of these are understudied or have no known function.

  The msf gene causes condition-specific shifts in global gene expression in Haemophilus influenzae · 2026 · DOI

• However, the role of msf in other conditions and its molecular function remain unknown.

  The msf gene causes condition-specific shifts in global gene expression in Haemophilus influenzae · 2026 · DOI

• However, due to the special anatomical barrier of the brain tissue, the application of oncolytic viruses is currently limited to the intracranial administration route, which restricts its clinical convenience and safety.

  Bacterial outer membrane vesicles encapsulating oncolytic virus for targeted nose-to-brain delivery · 2026 · DOI

• A majority (66%) of physicians used exchange transfusion for hyperleukocytosis, but white blood cell thresholds varied widely.

  Practice variability in the management of critical pertussis: a multicenter survey of pediatric intensivists in the Arabian Gulf Cooperation Council region · 2026 · DOI

• However, the current research in this field is still insufficient and in-depth, and many key issues and mechanisms need to be further elucidated.

  Outer membrane vesicles of Porphyromonas gingivalis: recent advances in pathogenicity and associated mechanisms · 2025 · DOI

• Despite growing recognition of their involvement in periodontal disease, the extent of OMV interactions with host tissues and polymicrobial communities remains unclear.

  The role and mechanism of bacterial outer membrane vesicles in the development of periodontitis · 2025 · DOI

• While Metagenomic Next-Generation Sequencing (mNGS) offers rapid and sensitive pathogen detection, its cost-effectiveness in postoperative neurosurgical patients in critical care settings remains underexplored.

  Cost-effectiveness analysis of metagenomic next-generation sequencing versus traditional bacterial cultures for postoperative central nervous system infections in critical care settings: a prospective pilot study · 2025 · DOI

• meningitidis have not been reported in China previously and are phylogenetically distinct from strains with the same STs in the NCBI GenBank database.

  Emerging Neisseria meningitidis ST-1466 and ST-11026 as urogenital pathogens in China · 2025 · DOI

• Also, the case indicates that traditional methods are insufficient for the etiological diagnosis needs of critical and severe patient populations, and timely use of mNGS should be recommended.

  Complex and severe infection in a 67-year-old liver transplant recipient due to Cunninghamella elegans, Bordetella bronchiseptica, and Pneumocystis jirovecii · 2025 · DOI

• Fusobacterium nucleatum in colorectal cancer (CRC) tissue is implicated at multiple stages of the disease, while the mechanisms underlying bacterial translocation and colonization remain incompletely understood.

  Fusobacterium nucleatum extracellular vesicles are enriched in colorectal cancer and facilitate bacterial adhesion · 2024 · DOI

• However, it remains unclear how the COVID-19 pandemic influenced the epidemiology of brain abscesses.

  Changes in the epidemiology of pediatric brain abscesses pre- and post-COVID-19 pandemic: a single-center study · 2024 · DOI

• Further, microbiologic techniques to determine CSF sterility suffer from poorly understood limitations leading to premature discontinuation of antibiotics risking further neurologic damage in vulnerable hosts.

  New and old lessons from a devastating case of neonatal E coli meningitis · 2024 · DOI

• Brain abscess caused by GAS is uncommon in pediatric infectious diseases, and GAS brain abscess without acute infectious symptoms has been rarely reported.

  Brain abscess caused by Streptococcus pyogenes with atypical symptoms: a case report and literature review · 2024 · DOI

• The exact roles of glycosylation in Neisseria remains to be determined, but increasing evidence suggests that glycan variability can be a strategy to evade the human immune system.

  Sweet complexity: O-linked protein glycosylation in pathogenic Neisseria · 2024 · DOI

• BACKGROUND: Neurological infection is an important cause of critical illness, yet little is known on the epidemiology of neurological infections requiring critical care.

  A retrospective analysis of 20,178 adult neurological infection admissions to United Kingdom critical care units from 2001 to 2020 · 2024 · DOI

• Whereas a high proportion of HCPs discuss maternal vaccinations with pregnant women, confidence in discussing maternal vaccinations is lacking and HCPs experience inadequate training to discuss maternal vaccinations with pregnant women.

  Insights into maternal pertussis vaccination counselling: a qualitative study on perspectives and experiences among midwives and gynaecologists in the Netherlands · 2024 · DOI

• influenzae causing invasive disease in lower-middle income settings, including Indonesia, are lacking.

  Whole-genome sequencing of non-typeable Haemophilus influenzae isolated from a tertiary care hospital in Surabaya, Indonesia · 2024 · DOI

• Importance: Few studies have examined the incidence of long-term disabilities due to bacterial meningitis in childhood with extended follow-up time and a nationwide cohort.

  Increased Risk of Long-Term Disabilities Following Childhood Bacterial Meningitis in Sweden · 2024 · DOI

• Data on transplacental antibody transfer on Tdap vaccination before 24 weeks' gestation remain scarce and are particularly relevant for preterm infants to increase the time interval for maternal antibody transfer.

  Maternal Pertussis Immunization and Immunoglobulin G Levels in Early- to Late-Term and Preterm Infants · 2024 · DOI

• The precise mechanism by which filamentous cell shape is regulated in the ΔdegP and ΔdegPΔamiAb mutants remains unclear. The study does not investigate the role of other factors that may contribute to OMV production.

  Periplasmic crowding and peptidoglycan hydrolase activity as drivers of outer membrane vesiculation in Acinetobacter baumannii · 2026 · DOI

• The mechanisms of OMV production remain poorly understood. The precise molecular pathways linking periplasmic crowding and PG recycling to OMV biogenesis remain unclear.

  Periplasmic crowding and peptidoglycan hydrolase activity as drivers of outer membrane vesiculation in Acinetobacter baumannii · 2026 · DOI

• Further investigation of the identified inhibitors for their potential as therapeutic options. Application of the screening approach to identify inhibitors for other types of toxins. Exploration of the potential of endogenous proteins/peptides as inhibitors for bacterial toxins.

  Novel endogenous protein-based strategies to inhibit clinically relevant bacterial AB-type toxins including pertussis toxin · 2026 · DOI

Most-cited papers in Bacterial Infections and Vaccines

• High Risk for Invasive Meningococcal Disease Among Patients Receiving Eculizumab (Soliris) Despite Receipt of Meningococcal Vaccine · MMWR Morbidity and Mortality Weekly Report · 2017 · 310 citations
• Safety and Immunogenicity of Heptavalent Pneumococcal Vaccine Conjugated to CRM197 in United States Infants · PEDIATRICS · 1998 · 294 citations
• Lumbar Puncture in Pediatric Bacterial Meningitis: Defining the Time Interval for Recovery of Cerebrospinal Fluid Pathogens After Parenteral Antibiotic Pretreatment · PEDIATRICS · 2001 · 290 citations
• Bacteria hijack a meningeal neuroimmune axis to facilitate brain invasion · Nature · 2023 · 203 citations
• Use of Serogroup B Meningococcal Vaccines in Adolescents and Young Adults: Recommendations of the Advisory Committee on Immunization Practices, 2015 · MMWR Morbidity and Mortality Weekly Report · 2015 · 196 citations
• Gram-negative enteric bacillary meningitis: A twenty-one-year experience · The Journal of Pediatrics · 1993 · 195 citations
• Twelve year outcomes following bacterial meningitis: further evidence for persisting effects · Archives of Disease in Childhood · 2000 · 187 citations
• Possible association between amniotic fluid micro‐organism infection and microflora in the mouth · BJOG An International Journal of Obstetrics & Gynaecology · 2002 · 173 citations
• Bacteriology of abscesses of the central nervous system: a multicentre prospective study. · BMJ · 1977 · 159 citations
• A Multi-Component Meningococcal Serogroup B Vaccine (4CMenB): The Clinical Development Program · Drugs · 2013 · 149 citations

Most recent work

• Meningococcal B Vaccine to Prevent Neisseria gonorrhoeae Infection · New England Journal of Medicine · 2026
• Use of the GSK MenACWY-CRM/MenB-4C Pentavalent Meningococcal Vaccine Among Persons Aged ≥10 Years: Recommendations of the Advisory Committee on Immunization Practices — United States, 2025 · MMWR Morbidity and Mortality Weekly Report · 2026
• Meningitis in Kent: Two young people dead and 11 seriously ill in outbreak · BMJ · 2026
• Meningitis: Fatal outbreak in Kent is less targeted strain B, officials confirm: Video 1 · BMJ · 2026
• National outbreak of pertussis in England (2023–2024) in the context of international resurgence · Archives of Disease in Childhood · 2026
• A controlled human infection model for symptomatic pertussis in North America using the pertactin-producing clinical isolate D420 · medRxiv · 2026
• Serogroup Switching in Neisseria meningitidis with Dual Antibiotic Resistance · New England Journal of Medicine · 2026
• Clusters of Invasive Haemophilus influenzae Type b Disease Among Adults Using Substances or Experiencing Homelessness or Housing Instability — Alaska, Oregon, and Washington, 2023─2025 · MMWR Morbidity and Mortality Weekly Report · 2026
• The Risk of Adverse Birth Outcomes Among Twin Pregnancies After Influenza and Pertussis Vaccinations During Pregnancy: A Data Linkage Study · BJOG An International Journal of Obstetrics & Gynaecology · 2026
• Diphtheria-tetanus-acellular pertussis vaccine safety in children under 7 years: a post-marketing analysis of the U.S. vaccine adverse event reporting system · Frontiers in Cellular and Infection Microbiology · 2026

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