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MSphere Feb 2024Rickettsiae are Gram-negative obligate intracellular parasites of numerous eukaryotes. Human pathogens of the transitional group (TRG), typhus group (TG), and spotted...
Rickettsiae are Gram-negative obligate intracellular parasites of numerous eukaryotes. Human pathogens of the transitional group (TRG), typhus group (TG), and spotted fever group (SFG) rickettsiae infect blood-feeding arthropods, have dissimilar clinical manifestations, and possess unique genomic and morphological attributes. Lacking glycolysis, rickettsiae pilfer numerous metabolites from the host cytosol to synthesize peptidoglycan and lipopolysaccharide (LPS). For LPS, O-antigen immunogenicity varies between SFG and TG pathogens; however, lipid A proinflammatory potential is unknown. We previously demonstrated that (TRG), (TG), and (SFG) produce lipid A with long 2' secondary acyl chains (C16 or C18) compared to short 2' secondary acyl chains (C12) in (SFG) lipid A. To further probe this structural heterogeneity and estimate a time point when shorter 2' secondary acyl chains originated, we generated lipid A structures for two additional SFG rickettsiae ( and ) utilizing fast lipid analysis technique adopted for use with tandem mass spectrometry (FLAT). FLAT allowed analysis of lipid A structure directly from host cell-purified bacteria, providing a substantial improvement over lipid A chemical extraction. FLAT-derived structures indicate SFG rickettsiae diverging after evolved shorter 2' secondary acyl chains. While 2' secondary acyl chain lengths do not distinguish pathogens from non-pathogens, analyses of LpxL late acyltransferases revealed discrete active sites and hydrocarbon rulers for long versus short 2' secondary acyl chain addition. Our collective data warrant determining lipid A inflammatory potential and how structural heterogeneity impacts lipid A-host receptor interactions.IMPORTANCEDeforestation, urbanization, and homelessness lead to spikes in Rickettsioses. Vector-borne human pathogens of transitional group (TRG), typhus group (TG), and spotted fever group (SFG) rickettsiae differ by clinical manifestations, immunopathology, genome composition, and morphology. We previously showed that lipid A (or endotoxin), the membrane anchor of Gram-negative bacterial lipopolysaccharide (LPS), structurally differs in (later-evolving SFG) relative to (basal SFG), (TG), and (TRG). As lipid A structure influences recognition potential in vertebrate LPS sensors, further assessment of lipid A structural heterogeneity is needed. Here, we sidestepped the difficulty of lipid A chemical extraction by utilizing fast lipid analysis technique adopted for use with tandem mass spectrometry, a new procedure for generating lipid A structures directly from host cell-purified bacteria. These data confirm that later-evolving SFG pathogens synthesize structurally distinct lipid A. Our findings impact interpreting immune responses to different pathogens and utilizing lipid A adjuvant or anti-inflammatory properties in vaccinology.
Topics: Humans; Lipid A; Lipopolysaccharides; Typhus, Epidemic Louse-Borne; Rickettsia; Spotted Fever Group Rickettsiosis
PubMed: 38259062
DOI: 10.1128/msphere.00609-23 -
The American Journal of Tropical... Jan 2024
Topics: Animals; Humans; Siphonaptera; Rickettsia typhi; Typhus, Endemic Flea-Borne; Rickettsia Infections; California; Rickettsia; Rickettsia felis
PubMed: 38109770
DOI: 10.4269/ajtmh.23-0742 -
The Brazilian Journal of Infectious... 2024Multisystem Inflammatory Syndrome in Children (MIS-C) presents with fever, fatigue, elevated inflammatory markers (acute phase reactants), and a history of exposure to...
Multisystem Inflammatory Syndrome in Children (MIS-C) presents with fever, fatigue, elevated inflammatory markers (acute phase reactants), and a history of exposure to SARS-CoV-2 or positive antibodies to SARS-CoV-2. As the COVID-19 pandemic unfolded, the risk of MIS-C in the pediatric population increased. However, exposure to other viruses and the presence of SARS-CoV-2 positive antibodies in children hospitalized for various pathogen-associated illnesses will also remain common and may complicate differential diagnoses with diseases endemic to the region such as rickettsial diseases. The objective was to highlight the desirability of medical personnel systematically incorporating rickettsiosis as a differential diagnosis for MIS-C when studying a child with fever, non-specific symptoms, and elevated inflammatory markers. In conclusion MIS-C should be considered in children with elevated inflammatory markers when there is a history of COVID-19 and they also meet criteria that have already been established by international agencies, such as CDC and WHO.
Topics: Child; Humans; Rickettsia rickettsii; Rickettsia typhi; Child, Hospitalized; Mexico; Pandemics; Fever; COVID-19; Systemic Inflammatory Response Syndrome
PubMed: 38070540
DOI: 10.1016/j.bjid.2023.103707 -
Infectious Disease Reports Oct 2023Murine typhus is an acute febrile illness caused by , an obligately intracellular Gram-negative coccobacillus. Rats () and their fleas () serve as the reservoir and... (Review)
Review
Murine typhus is an acute febrile illness caused by , an obligately intracellular Gram-negative coccobacillus. Rats () and their fleas () serve as the reservoir and vector of , respectively. Humans become infected when -infected flea feces are rubbed into flea bite wounds or onto mucous membranes. The disease is endemic throughout much of the world, especially in tropical and subtropical seaboard regions where rats are common. Murine typhus is reemerging as an important cause of febrile illness in Texas and Southern California, where an alternate transmission cycle likely involves opossums () and cat fleas (). Although primarily an undifferentiated febrile illness, a range of neurologic manifestations may occur, especially when treatment is delayed. Serology is the mainstay of diagnostic testing, but confirmation usually requires demonstrating seroconversion or a fourfold increase in antibody titer from acute- and convalescent-phase sera (antibodies are seldom detectable in the first week of illness). Thus, early empiric treatment with doxycycline, the drug of choice, is imperative. The purpose of this review is to highlight murine typhus as an important emerging and reemerging infectious disease, review its neurologic manifestations, and discuss areas in need of further study.
PubMed: 37987401
DOI: 10.3390/idr15060063 -
Case Reports in Infectious Diseases 2023Flea-borne typhus (FBT), an uncommon illness in the United States, typically presents as a high continuous fever with commonly associated symptoms including headache,...
BACKGROUND
Flea-borne typhus (FBT), an uncommon illness in the United States, typically presents as a high continuous fever with commonly associated symptoms including headache, myalgias, and rashes on the trunk and extremities. Patients infected with FBT may also present with atypical symptoms. As such, the combination of its relatively low incidence in the United States coupled with its variability in associated symptoms poses a diagnostic challenge for clinicians; early empiric treatment with doxycycline is warranted prior to a definitive diagnosis to reduce the risk of damage to vital organs. . This case describes a 54-year-old male who presented to an emergency room in Houston, Texas, with one week of constant right upper quadrant abdominal pain and fevers up to 40°C. The patient was initially diagnosed with Grade III severe acute cholangitis after abdominal ultrasound revealed gallbladder sludge and wall thickening without ductal dilatation, but a subsequent endoscopic retrograde cholangiopancreatography was unremarkable. Following intermittent fevers and worsening anemia, the patient was started on oral doxycycline for atypical infection, and an infectious disease workup subsequently returned a positive titer for . He experienced rapid symptomatic and clinical improvement, and the patient was discharged home with a final diagnosis of flea-borne typhus.
CONCLUSION
Albeit uncommon, the presentation of this patient's symptoms and final diagnosis of flea-borne typhus demonstrates the importance of (1) keeping atypical infections such as FBT in the differential diagnosis and (2) beginning empiric treatment to prevent damage to vital organs if suspicion of FBT is high.
PubMed: 37954983
DOI: 10.1155/2023/5510295 -
Emerging Infectious Diseases Nov 2023Murine typhus is a febrile, fleaborne disease caused by infection with Rickettsia typhi bacteria. Cases can range from mild and nonspecific to fatal. We report 2 cases...
Murine typhus is a febrile, fleaborne disease caused by infection with Rickettsia typhi bacteria. Cases can range from mild and nonspecific to fatal. We report 2 cases of murine typhus in Costa Rica, confirming the presence and circulation of R. typhi causing severe disease in the country.
Topics: Animals; Mice; Humans; Typhus, Endemic Flea-Borne; Costa Rica; Rickettsia typhi; Rickettsia
PubMed: 37877575
DOI: 10.3201/eid2911.221561 -
Microbiology Spectrum Dec 2023spp. are intracellular bacterial parasites of a wide range of arthropod and vertebrate hosts. Some rickettsiae are responsible for several severe human diseases...
Autophagy facilitates intracellular survival of pathogenic rickettsiae in macrophages via evasion of autophagosomal maturation and reduction of microbicidal pro-inflammatory IL-1 cytokine responses.
spp. are intracellular bacterial parasites of a wide range of arthropod and vertebrate hosts. Some rickettsiae are responsible for several severe human diseases globally. One interesting feature of these pathogens is their ability to exploit host cytosolic defense responses to their benefits. However, the precise mechanism by which pathogenic spp. elude host defense responses remains unclear. Here, we observed that pathogenic and (Sheila Smith [SS]), but not non-pathogenic , become ubiquitinated and induce autophagy upon entry into macrophages. Moreover, unlike , and (SS) colocalized with LC3B but not with Lamp2 upon host cell entry. Finally, we observed that both and (SS), but not , reduce pro-inflammatory interleukin-1 (IL-1) responses, likely via an autophagy-mediated mechanism. In summary, we identified a previously unappreciated pathway by which both pathogenic and (SS) become ubiquitinated, induce autophagy, avoid autolysosomal destruction, and reduce microbicidal IL-1 cytokine responses to establish an intracytosolic niche in macrophages.
Topics: Humans; Interleukin-1; Cytokines; Rickettsia; Macrophages; Autophagy
PubMed: 37819111
DOI: 10.1128/spectrum.02791-23 -
One Health (Amsterdam, Netherlands) Dec 2023Wild animal trade for human consumption is a global issue, involving complex interactions between economics, culture, food security and conservation. Whilst being a...
Wild animal trade for human consumption is a global issue, involving complex interactions between economics, culture, food security and conservation. Whilst being a biodiversity issue, it is also a major public health concern, with recent epidemics and pandemics of zoonotic pathogens linked to interactions with wildlife. At three time points, between March 2017 and June 2018, a longitudinal sero-survey of 150 market vendors from three wet markets in Laos (selling vegetables, domestic animal meat and/or wildlife meat) was conducted to determine if vendors had been differentially exposed to three endemic bacterial pathogens - , and spp. A total of 367 serum samples were tested by IgG enzyme-linked immunosorbent assay (ELISA) and immunofluorescence assay (IFA, for scrub typhus group (STG) and typhus group (TG) only). Among vendors, 32.7% were IgG-positive for at least one pathogen, 13.3% sero-converted during the study. Multi-season occupancy modelling for STG indicated a significantly higher prevalence of STG IgG in vegetable vendors (27.3%) and wildlife vendors (28.4%) than in domestic animal meat vendors (6.9 %, p=0.05), and higher in Phonsavanh market (OR=9.6, p=0.03) compared to Lak Sao and Salavan markets. Estimated mean incidence was 57 cases per 10,000 per 7.5-month period. For TG, vendor age had a significant effect on prevalence (OR=1.04, p=0.006), estimated mean incidence was 64 cases per 10,000 per season (7.5-month period). Despite individuals selling domestic meat having a higher prevalence of infections than those that did not (11.6% versus 4.5%), the difference was not significant. Whilst this study has a number of limitations, including vendors changing what food types they sold and no investigation of exposure outside of markets, the finding that the risk of exposure of vendors to zoonotic pathogens may be associated with types of food sold for human consumption warrants further investigation.
PubMed: 37811399
DOI: 10.1016/j.onehlt.2023.100618 -
Veterinary World Aug 2023Scrub typhus and murine typhus are globally distributed zoonoses caused by the intracellular Gram-negative bacteria and , respectively. Numerous studies have been...
BACKGROUND AND AIM
Scrub typhus and murine typhus are globally distributed zoonoses caused by the intracellular Gram-negative bacteria and , respectively. Numerous studies have been undertaken on rickettsial illnesses in humans and animals, including arthropod vectors, in Thailand. However, the reports on the seroprevalence of antibodies to and in buffaloes is extremely rare. Thus, this study aimed to estimate the seroprevalence of both rickettsial infections in water buffaloes () in Phatthalung Province, southern Thailand.
MATERIALS AND METHODS
From February to March 2023, a total of 156 serum samples were collected from 156 water buffaloes on 29 farms in Phatthalung province. The sera were screened for antibodies against and using an indirect immunofluorescence assay.
RESULTS
The seroprevalence of antibodies against and in individual water buffaloes was 4.49% (95% confidence interval [CI]: 2.19%-8.97%) and 3.85% (95% CI: 1.77%-8.14%), respectively, whereas 31% (9/29) of the herds had buffaloes with antibodies. The number of buffaloes with scrub typhus infection and ectoparasite infestation was statistically significant (p < 0.05; odds ratio = 6.25 [95% CI: 1.19-33.33]). Intriguingly, the prevalence of scrub typhus antibodies in buffaloes that were not infested with ectoparasites was much higher than those that were.
CONCLUSION
This is the first report of and antibodies in water buffalo sera in Southern Thailand. Two serum samples showed a high antibody titer against . Seroprevalence mainly occurred in non-ectoparasite-infested buffaloes, especially for antibodies. At the herd level, one-third of the studied farms showed seroprevalence. Additional research on the occurrence of these pathogens in vectors and in other animal reservoirs is necessary.
PubMed: 37766717
DOI: 10.14202/vetworld.2023.1600-1604 -
Life (Basel, Switzerland) Sep 2023Different vector-borne pathogens are present or have (re-)emerged in Croatia. Flaviviruses tick-borne encephalitis (TBEV), West Nile (WNV), and Usutu (USUV) are widely... (Review)
Review
Different vector-borne pathogens are present or have (re-)emerged in Croatia. Flaviviruses tick-borne encephalitis (TBEV), West Nile (WNV), and Usutu (USUV) are widely distributed in continental regions, while Toscana virus (TOSV) and sandfly fever viruses are detected at the Croatian littoral. Recently, sporadic clinical cases of Tahyna orthobunyavirus (TAHV) and Bhanja bandavirus infection and seropositive individuals have been reported in continental Croatia. Acute infections and serologic evidence of WNV, TBEV, USUV, and TAHV were also confirmed in sentinel animals and vectors. Autochthonous dengue was reported in 2010 at the Croatian littoral. Lyme borreliosis is the most widely distributed vector-borne bacterial infection. The incidence is very high in northwestern and eastern regions, which correlates with numerous records of ticks. Acute human infections are reported sporadically, but there are many records of serologic evidence of anaplasmosis in animals. Mediterranean spotted fever () and murine typhus () are the main rickettsial infections in Croatia. Human leishmaniasis is notified sporadically, while serologic evidence of leishmaniasis was found in 11.4% of the Croatian population. After the official eradication of malaria in 1964, only imported cases were reported in Croatia. Since vector-borne diseases show a growing trend, continuous monitoring of vectors is required to protect the population from these infections.
PubMed: 37763260
DOI: 10.3390/life13091856