Strategies used by <i>Leptospira</i> spirochetes to evade the host complement system

Barbosa, Angela Silva; Isaac, Lourdes

doi:10.1002/1873-3468.13768

Cited by 25 publications

(30 citation statements)

References 98 publications

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“…Although leptospiral LPS that is believed to be an adhesin for crawling induces the expression of proinflammatory cytokine genes through the recognition by the host TLR, the host-dependent difference in the TLR recognition was shown between human and murine cells: TLR1 and TLR2 predominantly mediate the activation in human cells, whereas TLR2 and TLR4 act for the recognition in mouse cells (Werts et al, 2001;Nahori et al, 2005). Pathogenic leptospires evade the host immunity through the interaction with the complement system (Barbosa and Isaac, 2020). Also, the binding of L. interrogans to thrombin inhibits fibrin coagulation, which results in hemorrhage (Fernandes et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

Crawling Motility on the Host Tissue Surfaces Is Associated With the Pathogenicity of the Zoonotic Spirochete Leptospira

Koizumi

Nakamura

2020

Front. Microbiol.

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Bacterial motility is crucial for many pathogenic species in the process of invasion and/or dissemination. The spirochete bacteria Leptospira spp. cause symptoms, such as hemorrhage, jaundice, and nephritis, in diverse mammals including humans. Although loss-of-motility attenuate the spirochete's virulence, the mechanism of the motilitydependent pathogenicity is unknown. Here, focusing on that Leptospira spp. swim in liquid and crawl on solid surfaces, we investigated the spirochetal dynamics on the host tissues by infecting cultured kidney cells from various species with pathogenic and nonpathogenic leptospires. We found that, in the case of the pathogenic leptospires, a larger fraction of bacteria attached to the host cells and persistently traveled long distances using the crawling mechanism. Our results associate the kinetics and kinematic features of the spirochetal pathogens with their virulence.

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Section: Discussionmentioning

confidence: 99%

Crawling Motility on the Host Tissue Surfaces Is Associated With the Pathogenicity of the Zoonotic Spirochete Leptospira

Koizumi

Nakamura

2020

Front. Microbiol.

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“…Leptospirosis, locally known as the rat-urine disease, is a re-emerging infectious zoonotic disease with a worldwide distribution [ 1 – 3 ]. In Malaysia, leptospirosis has been reported as early as in the 1920s among civilians and military troops [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

“…To date, at least 41,736 cases with 502 deaths have been recorded corresponding to an average of 16 cases per 100,000 population annually (data from Ministry of Health, Malaysia) [ 5 ]. Because of its global distribution, with greater incidence in resource-poor populations and countries, leptospirosis gains more attention [ 1 – 3 , 6 , 7 ]. Leptospira , the etiologic agent of this disease not only affects humans but also infects and habituates a wide range of animals.…”

Section: Introductionmentioning

confidence: 99%

Combined PCR and MAT improves the early diagnosis of the biphasic illness leptospirosis

et al. 2020

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The diagnosis of leptospirosis remains a challenge due to its non-specific symptoms and the biphasic nature of the illness. A comprehensive diagnosis that includes both molecular (polymerase chain reaction (PCR)) and serology is vital for early detection of leptospirosis and to avoid misdiagnosis. However, not all samples could be subjected to both tests (serology and molecular) due to budget limitation, infrastructure, and technical expertise at least in resource-limited countries. We evaluated the usefulness of testing the clinically suspected leptospirosis cases with both techniques on all samples collected from the patients on the day of admission. Among the 165 patient's blood/serum samples tested (from three hospitals in Central Malaysia), 43 (26%) showed positivity by microscopic agglutination test (MAT), 63 (38%) by PCR, while 14 (8%) were positive by both MAT and PCR. For PCR, we tested two molecular targets (lipL32 by qPCR and 16S rDNA or rrs by nested PCR) and detected lipL32 in 47 (29%) and rrs gene in 63 (38%) patients. The use of more than one target gene for PCR increased the detection rates. Hence, a highly sensitive multiplex PCR targeting more than one diagnostic marker is recommended for the early detection of Leptospira in suspected patients. When the frequencies for positivity detected either by MAT or PCR combined, leptospirosis was diagnosed in a total of 92 (56%) patients, a higher frequency compared to when samples were only tested by a single method (MAT or PCR). The results from this study suggest the inclusion of both serology and molecular methods for every first sample irrespective of the days post-onset of symptoms (DPO) collected from patients for early diagnosis of leptospirosis.

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“…Additional complement resistance mechanisms involve capturing plasminogen and secreting metalloproteases that cleave complement components ( 80 ). Plasmin is a tightly controlled protease that plays a central role in the fibrinolytic system by dissolving fibrin clots after wound repair.…”

Section: Evasion Of Innate Immunity Including Complementmentioning

confidence: 99%

Leptospiral Immunoglobulin-Like Domain Proteins: Roles in Virulence and Immunity

Haake

Matsunaga

2021

Front. Immunol.

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The virulence mechanisms required for infection and evasion of immunity by pathogenic Leptospira species remain poorly understood. A number of L. interrogans surface proteins have been discovered, lying at the interface between the pathogen and host. Among these proteins, the functional properties of the Lig (leptospiral immunoglobulin-like domain) proteins have been examined most thoroughly. LigA, LigB, and LigC contain a series of, 13, 12, and 12 closely related domains, respectively, each containing a bacterial immunoglobulin (Big) -like fold. The multidomain region forms a mostly elongated structure that exposes a large surface area. Leptospires wield the Lig proteins to promote interactions with a range of specific host proteins, including those that aid evasion of innate immune mechanisms. These diverse binding events mediate adhesion of L. interrogans to the extracellular matrix, inhibit hemostasis, and inactivate key complement proteins. These interactions may help L. interrogans overcome the physical, hematological, and immunological barriers that would otherwise prevent the spirochete from establishing a systemic infection. Despite significant differences in the affinities of the LigA and LigB proteins for host targets, their functions overlap during lethal infection of hamsters; virulence is lost only when both ligA and ligB transcription is knocked down simultaneously. Lig proteins have been shown to be promising vaccine antigens through evaluation of a variety of different adjuvant strategies. This review serves to summarize current knowledge of Lig protein roles in virulence and immunity and to identify directions needed to better understand the precise functions of the Lig proteins during infection.

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Strategies used by Leptospira spirochetes to evade the host complement system

Cited by 25 publications

References 98 publications

Crawling Motility on the Host Tissue Surfaces Is Associated With the Pathogenicity of the Zoonotic Spirochete Leptospira

Crawling Motility on the Host Tissue Surfaces Is Associated With the Pathogenicity of the Zoonotic Spirochete Leptospira

Combined PCR and MAT improves the early diagnosis of the biphasic illness leptospirosis

Leptospiral Immunoglobulin-Like Domain Proteins: Roles in Virulence and Immunity

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