Explore the vast range of titles available.

Rickettsial diseases have long been diagnosed with serum antibodies cross-reactive against Proteus vulgaris (Weil–Felix reaction). Although Weil–Felix antibodies are associated with the development of immunity, their rickettsial target and contribution to disease pathogenesis are not established. Here, we developed a transposon for insertional mutagenesis of Rickettsia conorii, isolating variants defective for replication in cultured cells and in spotted fever pathogenesis. Mutations in the polysaccharide synthesis operon (pso) abolish lipopolysaccharide O-antigen synthesis and Weil–Felix serology and alter outer-membrane protein assembly. Unlike wild-type R. conorii, pso mutants cannot elicit bactericidal antibodies that bind O antigen. The pso operon is conserved among rickettsial pathogens, suggesting that bactericidal antibodies targeting O antigen may generate universal immunity that could be exploited to develop vaccines against rickettsial diseases.

New human rickettsial pathogens have been discovered, and long-known rickettsiae of undetermined pathogenicity have been demonstrated to cause illness. Disease associated with Rickettsia slovaca has unique clinical manifestations, including prominent lymphadenopathy without fever and rash. Rickettsial genomes are highly conserved, with reductive evolution leading to a small genome that relies on the host cell for many biosynthetic functions. Advances in the evaluation of the pathogenesis of rickettsial disease include identification of rickettsial adhesins, a host cell receptor, signaling elements associated with entry of rickettsiae by induced phagocytosis, rickettsial enzymes mediating phagosomal escape, and host actin-based rickettsial cell-to-cell spread. Disruption of adherens junctions of infected endothelial cells likely plays a role in the critical pathophysiologic mechanism: increased microvascular permeability. Production of reactive oxygen species by infected endothelium injures these cells. However, disseminated intravascular coagulation rarely occurs. Immunity is mediated by reactive cytokine-activated rickettsicidal nitrogen and oxygen species and by clearance of rickettsiae by cytotoxic CD8 T cells.

Rickettsiosis is a re-emergent infectious disease without epidemiological surveillance in Colombia. This disease is generally undiagnosed and several deadly outbreaks have been reported in the country in the last decade. The aim of this study is to analyze the eco-epidemiological aspects of rickettsial seropositivity in rural areas of Colombia where outbreaks of the disease were previously reported. A cross-sectional study, which included 597 people living in 246 households from nine hamlets in two municipalities of Colombia, was conducted from November 2015 to January 2016. The survey was conducted to collect sociodemographic and household characteristics (exposure) data. Blood samples were collected to determine the rickettsial seropositivity in humans, horses and dogs (IFA, cut-off = 1/128). In addition, infections by rickettsiae were detected in ticks from humans and animals by real-time PCR targeting gltA and ompA genes. Data was analyzed by weighted multilevel clog-log regression model using three levels (person, household and hamlets) and rickettsial seropositivity in humans was the main outcome. Overall prevalence of rickettsial seropositivity in humans was 25.62% (95%CI 22.11-29.12). Age in years (PR = 1.01 95%CI 1.01-1.02) and male sex (PR = 1.65 95%CI 1.43-1.90) were risk markers for rickettsial seropositivity. Working outdoors (PR = 1.20 95%CI 1.02-1.41), deforestation and forest fragmentation for agriculture use (PR = 1.75 95%CI 1.51-2.02), opossum in peridomiciliary area (PR = 1.56 95%CI 1.37-1.79) and a high proportion of seropositive domestic animals in the home (PR20-40% vs <20% = 2.28 95%CI 1.59-3.23 and PR>40% vs <20% = 3.14 95%CI 2.43-4.04) were associated with rickettsial seropositivity in humans. This study showed the presence of Rickettsia antibodies in human populations and domestic animals. In addition, different species of rickettsiae were detected in ticks collected from humans and animals. Our results highlighted the role of domestic animals as sentinels of rickettsial infection to identify areas at risk of transmission, and the importance of preventive measures aimed at curtailing deforestation and the fragmentation of forests as a way of reducing the risk of transmission of emergent and re-emergent pathogens.

Infections caused by pathogenic species continue to scourge human health across the globe. From the point of entry at the site of transmission by arthropod vectors, hematogenous dissemination of rickettsiae occurs to diverse host tissues leading to ‘rickettsial vasculitis’ as the salient feature of pathogenesis. This perspective article accentuates recent breakthrough developments in the context of host–pathogen–vector interactions during rickettsial infections. The subtopics include potential exploitation of circulating macrophages for spread, identification of new entry mechanisms and regulators of actin-based motility, appreciation of metabolites acquired from and effectors delivered into the host, importance of the toxin–antitoxin module in host–cell interactions, effects of the vector microbiome on rickettsial transmission, and niche-specific riboregulation and adaptation. Further research on these aspects will advance our understanding of the biology of rickettsiae as intracellular pathogens and should enable design and development of new approaches to counter rickettsioses in humans and other hosts.

Background Rickettsioses, caused by intracellular bacteria of the genera Rickettsia and Orientia , are transmitted to humans through arthropod vectors such as ticks, fleas, and mites. Over the past two decades, this disease has been recognized as a significant cause of acute febrile illness in Sri Lanka. However, only a limited number of studies have focused on clinico-epidemiological characteristics of patients and immunological diagnostic approaches for disease confirmation. Method A cross-sectional study was conducted at the Rickettsial Disease Diagnostic and Research Laboratory (RDDRL), University of Kelaniya, Sri Lanka, from 2018 to 2023 from the clinically suspected patients referred for disease confirmation. Clinical, demographic, epidemiological, biochemical, and laboratory data were collected via a questionnaire by reviewing the archived records. The serological finding of the immunofluorescence assay (IFA) conducted for patients samples were retrieved. The patients who were positive for IFA-IgG (> 1:128 as per presumptive confirmation of acute rickettsial illness) were taken as the test group and the negative group was taken as the control group. Data were analyzed using chi-square tests followed by a Correlation analysis between the variables using Pearson correlation. Results Out of 1,221 cases, 249 (20.4%) were serologically “confirmed” as positive for rickettsial infection. The test group consisted predominantly of males, similar to the control group. Most cases were males and < 9 years of age followed by 10–19 years. Among the age groups, 10–19 years and 50–59 years, categories indicated a significant positive relationship according to the chi-squared statistics ( P  < 0.05). A seasonal trend was observed, with higher case numbers reported from January to February. Laboratory findings indicated significant differences between test and control groups in leucopenia ( P  = 0.005, χ²=7.87), increased neutrophil count ( P  = 0.0004, χ²=12.71), elevated alanine aminotransferase ( P  = 0.0001, χ²=14.64), elevated aspartate aminotransferase ( P  = 0.0001, χ²=18.24), urine occult blood ( P  = 0.024, χ²=5.09), and raised erythrocyte sedimentation rate ( P  = 0.034, χ²=4.51). Clinical manifestations showed no major deviations. Notably, eschar was more prevalent in O. tsutsugamushi cases (33.3%) compared to SFG rickettsioses (13.3%). Conclusion This study highlights the need for improved awareness, diagnostic facilities, and vector control measures to manage rickettsial infections effectively in Sri Lanka. Understanding epidemiological patterns and clinical manifestations is crucial for developing effective surveillance and prevention strategies. Clinical trial Not applicable.

Rickettsia are obligate intracellular bacteria that evade antimicrobial autophagy in the host cell cytosol by unknown mechanisms. Other cytosolic pathogens block different steps of autophagy targeting, including the initial step of polyubiquitin-coat formation. One mechanism of evasion is to mobilize actin to the bacterial surface. Here, we show that actin mobilization is insufficient to block autophagy recognition of the pathogen Rickettsia parkeri . Instead, R. parkeri employs outer membrane protein B (OmpB) to block ubiquitylation of the bacterial surface proteins, including OmpA, and subsequent recognition by autophagy receptors. OmpB is also required for the formation of a capsule-like layer. Although OmpB is dispensable for bacterial growth in endothelial cells, it is essential for R. parkeri to block autophagy in macrophages and to colonize mice because of its ability to promote autophagy evasion in immune cells. Our results indicate that OmpB acts as a protective shield to obstruct autophagy recognition, thereby revealing a distinctive bacterial mechanism to evade antimicrobial autophagy. Rickettsia surface protein OmpB promotes host colonization by blocking host ubiquitylation of bacterial surface proteins, thereby evading destruction by host autophagic processes.

Background Rickettsia felis and Rickettsia typhi are emerging arthropod-borne zoonoses causing fever and flu-like symptoms. Seroprevalence and risk factors associated with exposure to these organisms was explored in Australian veterinarians. Methods One hundred and thirty-one veterinarians from across Australia were recruited to participate in a cross-sectional survey. Veterinarians provided a single blood sample and answered a questionnaire on potential risk factors influencing their exposure to R. felis and R. typhi . Indirect microimmunofluorescence antibody testing (IFAT) was used to identify evidence of serological exposure of the participants to R. felis and R. typhi . Results were analyzed and a logistical regression model performed to predict risk factors associated with seropositivity. Results In total, 16.0% of participants were seropositive to R. felis , 4.6% to R. typhi and 35.1% seropositive to both, where cross-reactivity of the IFAT between R. felis and R. typhi precluded a definitive diagnosis. Veterinarians residing within the south-eastern states of Victoria and Tasmania were at a higher risk of exposure to R. felis or generalised R. felis or R. typhi exposure. Older veterinarians and those that recommended flea treatment to their clients were found to be significantly protected from exposure. Conclusions The high exposure to R. felis amongst veterinary professionals suggests that flea-borne spotted fever is an important cause of undifferentiated fever conditions that may not be adequately recognized in Australia.

Despite their high degree of genomic similarity, different spotted fever group (SFG) are often associated with very different clinical presentations. For example, causes Mediterranean spotted fever, a life-threatening disease for humans, whereas is associated with limited or no pathogenicity to humans. However, the molecular basis responsible for the different pathogenicity attributes are still not understood. Although killing microbes is a critical function of macrophages, the ability to survive and/or proliferate within phagocytic cells seems to be a phenotypic feature of several intracellular pathogens. We have previously shown that and exhibit different intracellular fates within macrophage-like cells. By evaluating early macrophage responses upon insult with each of these rickettsial species, herein we demonstrate that infection with results in a profound reprogramming of host gene expression profiles. Transcriptional programs generated upon infection with this pathogenic bacteria point toward a sophisticated ability to evade innate immune signals, by modulating the expression of several anti-inflammatory molecules. Moreover, induce the expression of several pro-survival genes, which may result in the ability to prolong host cell survival, thus protecting its replicative niche. Remarkably, -infection promoted a robust modulation of different transcription factors, suggesting that an early manipulation of the host gene expression machinery may be key to proliferation in THP-1 macrophages. This work provides new insights into the early molecular processes hijacked by a pathogenic SFG to establish a replicative niche in macrophages, opening several avenues of research in host-rickettsiae interactions.

Pathogenic Rickettsia species target vascular endothelial cells and cause systemic vasculitis. As obligate intracellular bacterial pathogens, Rickettsia must secure nutritional resources within the cytoplasm of endothelial cells while simultaneously subverting the innate immune defense system. With advances in rickettsial and host genetics, recent studies have identified novel molecular mechanisms involved in the complex interactions between Rickettsia and endothelial cells. However, it remains unclear how Rickettsia shields pathogen-derived immune stimulants, such as lipopolysaccharides (LPS) and peptidoglycan fragments, from immune recognition during intracellular replication. Prior work described two Rickettsia conorii variants with kkaebi transposon insertions in the polysaccharide synthesis operon ( pso ). Biochemical and immunological analyses revealed that pso is responsible for the biosynthesis of O-antigen (O-Ag) and the proper assembly of surface proteins. In the present work, we document that pso variant HK2 exhibits reduced capacities to adhere to and invade microvascular endothelial cells. Despite the low intracellular abundance, HK2 induced significantly higher levels of proinflammatory cytokines and chemokines, leading to premature cell death. Notably, HK2 exhibited defective intracellular survival in bone marrow-derived macrophages. This inability to dampen endothelial cell-mediated immune stimulation and resist macrophage-induced bactericidal activities resulted in the rapid elimination of viable Rickettsia in the mouse model of spotted fever. Further, when tested as a live-attenuated vaccine, HK2 elicited robust protective immunity against lethal spotted fever pathogenesis. Our work highlights the crucial role of pso in enabling Rickettsia to evade immune surveillance during intracellular replication within endothelial cells, ultimately delaying pathogen-induced programmed cell death and escaping immune defense mechanisms.

Diagnosis of rickettsial infections is challenging due to nonspecific clinical symptoms and limitations of current diagnostic methods. Molecular assays allow early detection but are limited by cost and technical demands, whereas conventional serological tests often exhibit cross-reactivity and low sensitivity during the early stages of infection. This study aimed to develop and evaluate a recombinant-antigen sandwich ELISA for improved antibody detection against Rickettsia spp. Three Rickettsia akari proteins, rGroEL, rDnaK, and rA8GP63 (uncharacterized protein), were produced and validated for immunogenicity. The assay was evaluated using 94 patient serum samples, including those with positive, negative, and unknown clinical course. The optimized ELISA demonstrated high reproducibility, with IgG sensitivity of 89.47–95.39% and specificity of 90%. IgM detection, also assessed, showed lower sensitivity (42.11–82.89%) but maintained strong specificity (83.33%). The diagnostic performance was comparable to that of a commercial indirect immunofluorescence assay, with no cross-reactivity detected in sera from patients with unrelated infections. rDnaK and rA8GP63 represent newly explored diagnostic candidates. These findings highlight the potential of this recombinant protein-based ELISA as an accessible, sensitive and specific diagnostic tool, with a meaningful clinical impact for improving the early and accurate detection of rickettsial infections.