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MSphere May 2021Species of (: ) are obligate intracellular parasites of a wide range of eukaryotes, with recognized arthropod-borne human pathogens belonging to the transitional group...
Species of (: ) are obligate intracellular parasites of a wide range of eukaryotes, with recognized arthropod-borne human pathogens belonging to the transitional group (TRG), typhus group (TG), and spotted fever group (SFG) rickettsiae. Growing in the host cytosol, rickettsiae pilfer numerous metabolites to make a typical Gram-negative bacterial cell envelope. The O-antigen of rickettsial lipopolysaccharide (LPS) is immunogenic and has been shown to tether the S-layer to the rickettsial surface; however, little is known about the structure and immunogenicity of the lipid A moiety. The structure of lipid A, the membrane anchor of LPS, affects the ability of this molecule to interact with components of the host innate immune system, specifically the MD-2/TLR4 receptor complex. To dissect the host responses that can occur during and infection, structural analysis of lipid A is needed. Lipid A was extracted from four species and structurally analyzed. (TRG), (TG), and (SFG) produced a similar structure, whereas (SFG) altered the length of a secondary acyl group. While all structures have longer acyl chains than known highly inflammatory hexa-acylated lipid A structures, the modification should differentially alter interactions with the hydrophobic internal pocket in MD2. The significance of these characteristics toward inflammatory potential as well as membrane dynamics between arthropod and vertebrate cellular environments warrants further investigation. Our work adds lipid A to the secretome and O-antigen as variable factors possibly correlating with phenotypically diverse rickettsioses. Spikes in rickettsioses occur as deforestation, urbanization, and homelessness increase human exposure to blood-feeding arthropods. Still, effective vaccines remain elusive. Recent studies have determined that lipopolysaccharide anchors the protective S-layer to the bacterial surface and elicits bactericidal antibodies. Furthermore, growing immunological evidence suggests vertebrate sensors (MD-2/TLR4 and noncanonical inflammasome) typically triggered by the lipid A portion of lipopolysaccharide are activated during infection. However, the immunopotency of lipid A is unknown due to poor appreciation for its structure. We determined lipid A structures for four distinct rickettsiae, revealing longer acyl chains relative to highly inflammatory bacterial lipid A. Surprisingly, lipid A of the Rocky Mountain spotted fever agent deviates in structure from other rickettsiae. Thus, lipid A divergence may contribute to variable disease phenotypes, sounding an alarm for determining its immunopotency and possible utility (i.e., as an adjuvant or anti-inflammatory) for development of more prudent rickettsiacidal therapies.
Topics: Humans; Lipid A; Rickettsia; Rickettsia Infections
PubMed: 33952661
DOI: 10.1128/mSphere.00184-21 -
Vaccines Sep 2022Outbreaks of life-threatening Rocky Mountain spotted fever in humans and dogs associated with a canine-tick maintenance cycle constitute an important One Health... (Review)
Review
Outbreaks of life-threatening Rocky Mountain spotted fever in humans and dogs associated with a canine-tick maintenance cycle constitute an important One Health opportunity. The reality of the problem has been observed strikingly in Mexico, Brazil, Colombia, and Native American tribal lands in Arizona. The brown dog tick, , acquires the rickettsia from bacteremic dogs and can maintain the bacterium transtadially to the next tick stage. The subsequent adult tick can then transmit infection to a new host, as shown by guinea pig models. These brown dog ticks maintain spotted fever group rickettsiae transovarially through many generations, thus serving as both vector and reservoir. Vaccine containing whole-killed does not stimulate sufficient immunity. Studies of subunit antigens have demonstrated that conformationally preserved outer-membrane autotransporter proteins A and B are the leading vaccine candidates. The possibility of a potentially safe and effective live attenuated vaccine has only begun to be explored as gene knockout methods are applied to these obligately intracellular pathogens.
PubMed: 36298491
DOI: 10.3390/vaccines10101626 -
Ticks and Tick-borne Diseases Mar 2023Rickettsioses are vector-borne zoonotic diseases whose etiological agents are bacteria of the genera Rickettsia and Orientia. In Colombia, literature published on...
Rickettsioses are vector-borne zoonotic diseases whose etiological agents are bacteria of the genera Rickettsia and Orientia. In Colombia, literature published on rickettsioses during the 20th century is limited and disperse; to date, there are no detailed publications that compile the affected regions or the involved Rickettsia species in each outbreak. Since early works of Luis Patiño-Camargo, the study of rickettsioses gained major importance with the subsequent description of significant outbreaks in some departments of the country. During the 1940s, many articles were published reporting outbreaks probably caused by Rickettsia rickettsii, Rickettsia typhi, and Rickettsia prowazekii, as well as studies on their diagnosis, vaccination, and prophylaxis. One of the most notorious works was published by Patiño-Camargo where he named the R. rickettsii rickettsiosis as "Tobia fever". However, in the subsequent decades, these entities entered a prolonged period of neglected research and surveillance, and just gained importance until the 21st century, when new fatal cases began to be reported in the country; thus, many questions remained unanswered during this overlooked period. The present work reviewed online databases, repositories, and libraries to compile literature related to rickettsioses in Colombia published during the 20th century. Gathered data show that typhus group rickettsioses (including infections by R. typhi and R. prowazekii) were broadly distributed in departments from the Andean and Caribbean regions, and that spotted fever group rickettsioses cases (including infections by R. rickettsii) were registered in other locations different from Tobia (Cundinamarca), like Atlántico, Bolivar, and Santander departments. These findings contribute to the knowledge of these diseases, their historical distribution, public health burden, and set new horizons for rickettsioses research in different Colombian locations.
Topics: Male; Humans; Colombia; Rickettsia Infections; Rickettsia; Rickettsia prowazekii; Rickettsia rickettsii
PubMed: 36628901
DOI: 10.1016/j.ttbdis.2022.102118 -
Infection and Immunity Mar 2021, the etiological agent of Rocky Mountain spotted fever (RMSF), a life-threatening tick-borne disease that affects humans and various animal species, has been recognized...
, the etiological agent of Rocky Mountain spotted fever (RMSF), a life-threatening tick-borne disease that affects humans and various animal species, has been recognized in medicine and science for more than 100 years. Isolate-dependent differences in virulence of have been documented for many decades; nonetheless, the specific genetic and phenotypic factors responsible for these differences have not been characterized. Using and methods, we identified multiple phenotypic differences among six geographically distinct isolates of , representing isolates from the United States, Costa Rica, and Brazil. Aggregate phenotypic data, derived from growth in Vero E6 cells and from clinical and pathological characteristics following infection of male guinea pigs (), allowed separation of these isolates into three categories: nonvirulent (Iowa), mildly virulent (Sawtooth and Gila), and highly virulent (Sheila Smith, Costa Rica, and Taiaçu). Transcriptional profiles of 11 recognized or putative virulence factors confirmed the isolate-dependent differences between mildly and highly virulent isolates. These data corroborate previous qualitative assessments of strain virulence and suggest further that a critical and previously underappreciated balance between bacterial growth and host immune response could leverage strain pathogenicity. Also, this work provides insight into isolate-specific microbiological factors that contribute to the outcome of RMSF and confirms the hypothesis that distinct rickettsial isolates also differ phenotypically, which could influence the severity of disease in vertebrate hosts.
Topics: Animals; Bacterial Load; Biomarkers; Disease Models, Animal; Disease Susceptibility; Gene Expression Regulation, Bacterial; Guinea Pigs; Host-Pathogen Interactions; Humans; Immunohistochemistry; Male; Rickettsia rickettsii; Rocky Mountain Spotted Fever; Symptom Assessment; Virulence; Virulence Factors
PubMed: 33495273
DOI: 10.1128/IAI.00626-20 -
Microbiology Resource Announcements Oct 2023Complete genomes of were sequenced with Illumina and PacBio technologies from low-passage isolates from ticks. These isolates were quality controlled for intact , a...
Complete genomes of were sequenced with Illumina and PacBio technologies from low-passage isolates from ticks. These isolates were quality controlled for intact , a regulator of actin-based motility that is negatively selected for in culture. The Sheila Smith strain was re-sequenced using the same methodology.
PubMed: 37655895
DOI: 10.1128/MRA.00362-23 -
Frontiers in Cellular and Infection... 2017Ticks transmit a greater variety of pathogenic agents that cause disease in humans and animals than any other haematophagous arthropod, including Lyme disease, Rocky... (Review)
Review
Ticks transmit a greater variety of pathogenic agents that cause disease in humans and animals than any other haematophagous arthropod, including Lyme disease, Rocky Mountain spotted fever, human granulocytic anaplasmosis, babesiosis, tick-borne encephalitis, Crimean Congo haemorhagic fever, and many others (Gulia-Nuss et al., 2016). Although diverse explanations have been proposed to explain their remarkable vectorial capacity, among the most important are their blood feeding habit, their long term off-host survival, the diverse array of bioactive molecules that disrupt the host's natural hemostatic mechanisms, facilitate blood flow, pain inhibitors, and minimize inflammation to prevent immune rejection (Hajdušek et al., 2013). Moreover, the tick's unique intracellular digestive processes allow the midgut to provide a relatively permissive microenvironment for survival of invading microbes. Although tick-host-pathogen interactions have evolved over more than 300 million years (Barker and Murrell, 2008), few microbes have been able to overcome the tick's innate immune system, comprising both humoral and cellular processes that reject them. Similar to most eukaryotes, the signaling pathways that regulate the innate immune response, i.e., the Toll, IMD (Immunodeficiency) and JAK-STAT (Janus Kinase/ Signal Transducers and Activators of Transcription) also occur in ticks (Gulia-Nuss et al., 2016). Recognition of pathogen-associated molecular patterns (PAMPs) on the microbial surface triggers one or the other of these pathways. Consequently, ticks are able to mount an impressive array of humoral and cellular responses to microbial challenge, including anti-microbial peptides (AMPs), e.g., defensins, lysozymes, microplusins, etc., that directly kill, entrap or inhibit the invaders. Equally important are cellular processes, primarily phagocytosis, that capture, ingest, or encapsulate invading microbes, regulated by a primordial system of thioester-containing proteins, fibrinogen-related lectins and convertase factors (Hajdušek et al., 2013). Ticks also express reactive oxygen species (ROS) as well as glutathione-S-transferase, superoxide dismutase, heat shock proteins and even protease inhibitors that kill or inhibit microbes. Nevertheless, many tick-borne microorganisms are able to evade the tick's innate immune system and survive within the tick's body. The examples that follow describe some of the many different strategies that have evolved to enable ticks to transmit the agents of human and/or animal disease.
Topics: Anaplasma phagocytophilum; Animals; Babesia microti; Borrelia burgdorferi; Host-Pathogen Interactions; Humans; Immunity, Innate; Rickettsia rickettsii; Tick-Borne Diseases; Ticks
PubMed: 28929088
DOI: 10.3389/fcimb.2017.00390 -
Frontiers in Cellular and Infection... 2013Spotted-fever-caused Rickettsia rickettsii infection is in Brazil the major tick-borne zoonotic disease. Recently, a second and milder human rickettsiosis caused by an... (Review)
Review
Spotted-fever-caused Rickettsia rickettsii infection is in Brazil the major tick-borne zoonotic disease. Recently, a second and milder human rickettsiosis caused by an agent genetically related to R. parkeri was discovered in the country (Atlantic rainforest strain). Both diseases clearly have an ecological background linked to a few tick species and their environment. Capybaras (Hydrochoerus hydrochaeris) and Amblyomma cajennense ticks in urban and rural areas close to water sources are the main and long-known epidemiological feature behind R. rickettsii-caused spotted-fever. Unfortunately, this ecological background seems to be increasing in the country and disease spreading may be foreseen. Metropolitan area of São Paulo, the most populous of the country, is embedded in Atlantic rainforest that harbors another important R. rickettsii vector, the tick Amblyomma aureolatum. Thus, at the city-forest interface, dogs carry infected ticks to human dwellings and human infection occurs. A role for R. rickettsii vectoring to humans of a third tick species, Rhipicephalus sanguineus in Brazil, has not been proven; however, there is circumstantial evidence for that. A R. parkeri-like strain was found in A. ovale ticks from Atlantic rainforest and was shown to be responsible for a milder febrile human disease. Rickettsia-infected A. ovale ticks are known to be spread over large areas along the Atlantic coast of the country, and diagnosis of human infection is increasing with awareness and proper diagnostic tools. In this review, ecological features of the tick species mentioned, and that are important for Rickettsia transmission to humans, are updated and discussed. Specific knowledge gaps in the epidemiology of such diseases are highlighted to guide forthcoming research.
Topics: Animals; Brazil; Ecology; Humans; Ixodidae; Phylogeography; Rickettsia; Rocky Mountain Spotted Fever; Topography, Medical
PubMed: 23875178
DOI: 10.3389/fcimb.2013.00027 -
Socio-ecological determinants of rickettsial seroprevalence in a rural community of Yucatán, Mexico.Infection, Genetics and Evolution :... Aug 2022Rickettsial diseases have seen a re-emergence in the Americas in the last few decades, with concerning morbidity, mortality and economic implications that result from...
Rickettsial diseases have seen a re-emergence in the Americas in the last few decades, with concerning morbidity, mortality and economic implications that result from loss of productivity, income, curbs in liberal trade agreements, and reduction in agricultural practices. The aim of this study is to determine the socioecological determinants and seroprevalence for Rickettsia typhi and Rickettsia rickettsii among residents of Teabo, a rural community of Yucatán, Mexico. Sociodemographic data and serum samples were obtained from 180 consenting participants. Antibody titers for R. typhi and R. rickettsii were determined by indirect immunofluorescence assay (IFA). Participants also submitted tick samples collected from their residential area. We conducted logistic regression models to evaluate the association between exposure variables and seroprevalence. Rhipicephalus sanguineus s.l. (37%; n = 65), and Amblyomma cajennense Fabricius (17%; n = 29) were the predominant tick species in peri-domestic areas. Out of the 180 participants, there was significantly higher seroprevalence of R. typhi (n = 77; 46%) compared to R. rickettsii [n = 27, 15%, (p < 0.05)]. Pearson's chi-square test of independence revealed significant differences in R. rickettsii seroprevalence by gender (X [n = 175, df = 4, (p < 0.001)] = 180.26), level of education, (X [n = 180, df = 4, (p < 0.001)] = 44.0), and by tick species found in residential area, (X [n = 180, df = 4, (p = 0.050)] = 9.48). After adjusting for other variables in a logistic regression model, for each unit increase in the number of dogs present in the residential area, there was a 27% increase in the odds of human seroprevalence for R. typhi IgG (AOR = 1.27, 95% CI: 1.01-1.63). Compared to study participants living in residential areas with a 'low' height of vegetation, those living in residential areas with a 'medium' height of vegetation had 2.5 times greater odds of human seroprevalence for R. typhi IgG (AOR = 2.51, 95% CI: 1.19-5.40). Potentially modifiable existing factors in the peri-domestic area may constitute a high-risk source of seroprevalence for rickettsial antibodies among residents of the rural community of Teabo, Yucatán, Mexico.
Topics: Animals; Dog Diseases; Dogs; Humans; Immunoglobulin G; Mexico; Rhipicephalus sanguineus; Rickettsia; Rural Population; Seroepidemiologic Studies
PubMed: 35490957
DOI: 10.1016/j.meegid.2022.105291 -
PLoS Pathogens Jul 2023Members of the spotted fever group rickettsia express four large, surface-exposed autotransporters, at least one of which is a known virulence determinant....
Members of the spotted fever group rickettsia express four large, surface-exposed autotransporters, at least one of which is a known virulence determinant. Autotransporter translocation to the bacterial outer surface, also known as type V secretion, involves formation of a β-barrel autotransporter domain in the periplasm that inserts into the outer membrane to form a pore through which the N-terminal passenger domain is passed and exposed on the outer surface. Two major surface antigens of Rickettsia rickettsii, are known to be surface exposed and the passenger domain cleaved from the autotransporter domain. A highly passaged strain of R. rickettsii, Iowa, fails to cleave these autotransporters and is avirulent. We have identified a putative peptidase, truncated in the Iowa strain, that when reconstituted into Iowa restores appropriate processing of the autotransporters as well as restoring a modest degree of virulence.
Topics: Rickettsia rickettsii; Type V Secretion Systems; Peptide Hydrolases; Bacterial Outer Membrane Proteins; Virulence Factors
PubMed: 37523399
DOI: 10.1371/journal.ppat.1011527 -
Microorganisms Jun 2020Ticks are obligate hematophagous arthropods and act as vectors for a great variety of pathogens, including viruses, bacteria, protozoa, and helminths. Some tick-borne... (Review)
Review
Ticks are obligate hematophagous arthropods and act as vectors for a great variety of pathogens, including viruses, bacteria, protozoa, and helminths. Some tick-borne viruses, such as Powassan virus and tick-borne encephalitis virus, are transmissible within 15-60 min after tick attachment. However, a minimum of 3-24 h of tick attachment is necessary to effectively transmit bacterial agents such as spp., spp., and spp. to a new host. Longer transmission periods were reported for spp. and protozoans such as spp., which require a minimum duration of 24-48 h of tick attachment for maturation and migration of the pathogen. Laboratory observations indicate that the probability of transmission of tick-borne pathogens increases with the duration an infected tick is allowed to remain attached to the host. However, the transmission time may be shortened when partially fed infected ticks detach from their initial host and reattach to a new host, on which they complete their engorgement. For example, early transmission of tick-borne pathogens (e.g., , , and ) and a significantly shorter transmission time were demonstrated in laboratory experiments by interrupted blood feeding. The relevance of such situations under field conditions remains poorly documented. In this review, we explore parameters of, and causes leading to, spontaneous interrupted feeding in nature, as well as the effects of this behavior on the minimum time required for transmission of tick-borne pathogens.
PubMed: 32560202
DOI: 10.3390/microorganisms8060910