The neglected challenge: Vaccination against rickettsiae

Osterloh, Anke

doi:10.1371/journal.pntd.0008704

Cited by 14 publications

(13 citation statements)

References 204 publications

(436 reference statements)

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“…As with other Rickettsioses, doxycycline is the treatment of choice although its effect weakens later in infection. Effective vaccines do not exist (Osterloh, 2020).…”

Section: Introductionmentioning

confidence: 99%

Rickettsia typhi peptidoglycan mapping with data-dependent tandem mass spectrometry

Oyler

Rennoll-Bankert

Verhoeve

et al. 2022

Preprint

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Rickettsia species are diverse Gram-negative obligate intracellular bacteria often pervasive in numerous invertebrates, as well as fungal, nematode and microeukaryotic hosts. Certain species are etiological agents for well-known arthropod-borne illnesses; e.g., R. rickettsii (Rocky Mountain Spotted Fever), R. prowazekii (Epidemic Typhus), and R. typhi, (Endemic Typhus). Living freely in eukaryotic cytosol presumably exposes rickettsiae to host cell immune receptors, particularly those recognizing bacterial cell envelope glycoconjugates. However, the mechanics of host recognition of rickettsiae remain poorly defined. As rickettsiae synthesize a canonical Gram-negative cell envelope that includes peptidoglycan (PGN) and lipopolysaccharide (LPS), structural insight on these macromolecules is important for deciphering host responses to these pathogens. In this work, PGN from R. typhi was digested and the resultant subunits were analyzed by two different, albeit complementary, sample preparation methods. Both approaches were subsequently subjected to liquid chromatography/mass spectrometry analysis to infer PGN structure. R. typhi PGN was determined to be similar to most other Gram-negative bacteria, with mDAP-type muropeptide subunits. However, additional alanine residues were observed elongating the muropeptide stems, rather than the glycine residues usually observed in Gram-negative bacterial PGN. Despite this deviation, R. typhi contains a murein layer that is predicted to agonize host cellular PGN receptors and be susceptible to PGN-targeting antimicrobials. This same structure is likely synthesized by all Rickettsia species, as bioinformatics and comparative genomics analyses indicate the biosynthesis of PGN is highly conserved. Determining how host cells process this canonical glycoconjugate during infection is crucial for identifying factors behind rickettsial pathogenesis, including immunoavoidance or proinflammatory mechanisms possibly employed by rickettsiae with varying pathogenic potential.

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“…As with other Rickettsioses, doxycycline is the treatment of choice although its effect weakens later in infection. Effective vaccines do not exist (Osterloh, 2020).…”

Section: Introductionmentioning

confidence: 99%

Rickettsia typhi peptidoglycan mapping with data-dependent tandem mass spectrometry

Oyler

Rennoll-Bankert

Verhoeve

et al. 2022

Preprint

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“…This approach should be the choice for high-risk travellers, such as backpackers, trekkers, and cave explorers, especially in areas where access to a medical facility is limited. Currently, vaccination against rickettsiosis has been investigated in an experimental animal model [40]. Unfortunately, to date, there is no promising human vaccine in the drug pipeline.…”

Section: Travel-associated Rickettsiosismentioning

confidence: 99%

Rickettsiosis in Southeast Asia: Summary for International Travellers during the COVID-19 Pandemic

2022

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Rickettsiosis is an important cause of febrile illness among travellers visiting Southeast Asia (SEA). The true incidence of rickettsiosis is underestimated; however, murine typhus and scrub typhus are widely distributed across SEA. Among travellers visiting SEA, scrub typhus was mostly reported from Thailand, whereas murine typhus was frequently found in Indonesia. Although most cases are self-limited or present with mild symptoms, a few cases with severe clinical manifestations have been reported. Doxycycline remains the key treatment of rickettsiosis. Some travellers, such as backpackers, trekkers, or cave explorers, are at a higher risk for rickettsiosis than others. Therefore, in resource-limited conditions, empirical treatment should be considered in these travellers. The coronavirus disease 2019 (COVID-19) pandemic has contributed to difficulty in the diagnosis of rickettsiosis because of the clinical similarities between these diseases. In addition, physical distancing mandated by COVID-19 management guidelines limits accurate physical examination, resulting in misdiagnosis and delayed treatment of rickettsiosis. This review summarises the characteristics of murine typhus and scrub typhus, describes travel-associated rickettsiosis, and discusses the impact of the COVID-19 pandemic on rickettsiosis.

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“…There are currently no vaccines commercially available for rickettsioses [141]. Previous attempts for R. conorii vaccine development failed to provide long lasting immunity [142].…”

Section: Preventionmentioning

confidence: 99%

Mediterranean Spotted Fever: Current Knowledge and Recent Advances

Spernovasilis

Markaki²,

Papadakis

et al. 2021

TropicalMed

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Mediterranean spotted fever (MSF) is an emerging tick-borne rickettsiosis of the spotted fever group (SFG), endemic in the Mediterranean basin. By virtue of technological innovations in molecular genetics, it has been determined that the causative agent of MSF is Rickettsia conorii subspecies conorii. The arthropod vector of this bacterium is the brown dog tick Rhipicephalus sanguineus. The true nature of the reservoir of R. conorii conorii has not been completely deciphered yet, although many authors theorize that the canine population, other mammals, and the ticks themselves could potentially contribute as reservoirs. Typical symptoms of MSF include fever, maculopapular rash, and a characteristic eschar (“tache noire”). Atypical clinical features and severe multi-organ complications may also be present. All of these manifestations arise from the disseminated infection of the endothelium by R. conorii conorii. Several methods exist for the diagnosis of MSF. Serological tests are widely used and molecular techniques have become increasingly available. Doxycycline remains the treatment of choice, while preventive measures are focused on modification of human behavior and vector control strategies. The purpose of this review is to summarize the current knowledge on the epidemiology, pathogenesis, clinical features, diagnosis, and treatment of MSF.

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The neglected challenge: Vaccination against rickettsiae

Cited by 14 publications

References 204 publications

Rickettsia typhi peptidoglycan mapping with data-dependent tandem mass spectrometry

Rickettsia typhi peptidoglycan mapping with data-dependent tandem mass spectrometry

Rickettsiosis in Southeast Asia: Summary for International Travellers during the COVID-19 Pandemic

Mediterranean Spotted Fever: Current Knowledge and Recent Advances

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