Faculty Opinions recommendation of Mycobacterium tuberculosis produces pili during human infection.

Author(s):  
Rino Rappuoli
2003 ◽  
Vol 10 (1) ◽  
pp. 88-94 ◽  
Author(s):  
Josephine Anne D. Navoa ◽  
Suman Laal ◽  
Liise-Anne Pirofski ◽  
Gary R. McLean ◽  
Zhongdong Dai ◽  
...  

ABSTRACT Arabinomannan (AM) is a polysaccharide antigen of the mycobacterial capsule. However, it is uncertain whether AM constitutes an immunologically distinct fraction of Mycobacterium tuberculosis. In this study, we analyzed the repertoire and specificity of antibodies to AM by using AM-binding murine monoclonal antibodies (MAbs) and human serum samples. Murine MAbs were found to be diverse in their specificity to AM and cross-reactivity with other arabinose-containing mycobacterial polysaccharides, with MAb 9d8 binding exclusively to AM. Human antibodies to AM were detected in serum samples from patients with pulmonary tuberculosis (TB), as well as in those from healthy, purified protein derivative-negative controls, with significantly higher titers among patients. The binding of human antibodies to AM was inhibited by MAb 9d8 in three patients with TB but not in controls. MAb 5c11, which recognizes other mycobacterial arabinose-containing carbohydrates in addition to AM, inhibited the binding of serum samples from 75% of patients and 76% of controls. Analysis of human antibodies with murine MAbs to human VH determinants demonstrated diversity among antibodies to AM with qualitative and quantitative differences compared with antibodies to lipoarabinomannan. In summary, our study suggests that antibodies to AM are diverse and heterogeneous with respect to antigen recognition and VH determinant expression, with human serum samples containing different subsets of antibodies to AM with the specificities of AM-binding murine MAbs. One MAb and a subset of human antibodies bind AM specifically, suggesting that this polysaccharide is antigenically distinct and is expressed in human infection.


2015 ◽  
Vol 84 (2) ◽  
pp. 502-510 ◽  
Author(s):  
Jannike Blank ◽  
Jochen Behrends ◽  
Thomas Jacobs ◽  
Bianca E. Schneider

Cerebral malaria (CM) is the most severe complication of human infection withPlasmodium falciparum. The mechanisms predisposing to CM are still not fully understood. Proinflammatory immune responses are required for the control of blood-stage malaria infection but are also implicated in the pathogenesis of CM. A fine balance between pro- and anti-inflammatory immune responses is required for parasite clearance without the induction of host pathology. The most accepted experimental model to study human CM isPlasmodium bergheiANKA (PbANKA) infection in C57BL/6 mice that leads to the development of a complex neurological syndrome which shares many characteristics with the human disease. We applied this model to study the outcome ofPbANKA infection in mice previously infected withMycobacterium tuberculosis, the causative agent of tuberculosis. Tuberculosis is coendemic with malaria in large regions in the tropics, and mycobacteria have been reported to confer some degree of unspecific protection against rodentPlasmodiumparasites in experimental coinfection models. We found that concomitantM. tuberculosisinfection did not change the clinical course ofPbANKA-induced experimental cerebral malaria (ECM) in C57BL/6 mice. The immunological environments in spleen and brain did not differ between singly infected and coinfected animals; instead, the overall cytokine and T cell responses in coinfected mice were comparable to those in animals solely infected withPbANKA. Our data suggest thatM. tuberculosiscoinfection is not able to change the outcome ofPbANKA-induced disease, most likely because the inflammatory response induced by the parasite rapidly dominates in mice previously infected withM. tuberculosis.


2005 ◽  
Vol 187 (19) ◽  
pp. 6726-6732 ◽  
Author(s):  
Hasan Yesilkaya ◽  
Jeremy W. Dale ◽  
Norval J. C. Strachan ◽  
Ken J. Forbes

ABSTRACT Transposable elements can affect an organism's fitness through the insertional inactivation of genes and can therefore be used to identify genes that are nonessential for growth in vitro or in animal models. However, these models may not adequately represent the genetic requirements during chains of human infection. We have therefore conducted a genome-wide survey of transposon mutations in Mycobacterium tuberculosis isolates from cases of human infection, identifying the precise, base-specific insertion sites of the naturally occurring transposable element IS6110. Of 294 distinct insertions mapped to the strain H37Rv genome, 180 were intragenic, affecting 100 open reading frames. The number of genes carrying IS6110 in clinical isolates, and hence apparently not essential for infection and transmission, is very much lower than the estimates of nonessential genes derived from in vitro studies. This suggests that most genes in M. tuberculosis play a significant role in human infection chains. IS6110 insertions were underrepresented in genes associated with virulence, information pathways, lipid metabolism, and membrane proteins but overrepresented in multicopy genes of the PPE family, genes of unknown function, and intergenic sequences. Population genomic analysis of isolates recovered from an organism's natural habitat is an important tool for determining the significance of genes or classes of genes in the natural biology of an organism.


2007 ◽  
Vol 104 (12) ◽  
pp. 5145-5150 ◽  
Author(s):  
C. J. Alteri ◽  
J. Xicohtencatl-Cortes ◽  
S. Hess ◽  
G. Caballero-Olin ◽  
J. A. Giron ◽  
...  

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Mariko Hakamata ◽  
Hayato Takihara ◽  
Tomotada Iwamoto ◽  
Aki Tamaru ◽  
Atsushi Hashimoto ◽  
...  

Abstract Mycobacterium tuberculosis (Mtb) strains of Beijing lineage have caused great concern because of their rapid emergence of drug resistance and worldwide spread. DNA mutation rates that reflect evolutional adaptation to host responses and the appearance of drug resistance have not been elucidated in human-infected Beijing strains. We tracked and obtained an original Mtb isolate of Beijing lineage from the 1999 tuberculosis outbreak in Japan, as well as five other isolates that spread in humans, and two isolates from the patient caused recurrence. Three isolates were from patients who developed TB within one year after infection (rapid-progressor, RP), and the other three isolates were from those who developed TB more than one year after infection (slow-progressor, SP). We sequenced genomes of these isolates and analyzed the propensity and rate of genomic mutations. Generation time versus mutation rate curves were significantly higher for RP. The ratio of oxidative versus non-oxidation damages induced mutations was higher in SP than RP, suggesting that persistent Mtb are exposed to oxidative stress in the latent state. Our data thus demonstrates that higher mutation rates of Mtb Beijing strains during human infection is likely to account for the higher adaptability and an emergence ratio of drug resistance.


1998 ◽  
Vol 36 (4) ◽  
pp. 1101-1102 ◽  
Author(s):  
Rita M. Washko ◽  
Heidi Hoefer ◽  
Timothy E. Kiehn ◽  
Donald Armstrong ◽  
Guy Dorsinville ◽  
...  

Mycobacterium tuberculosis was isolated from the eyelid, skin, tongue, and lungs of a green-winged macaw (Ara chloroptera). Two persons living in the same household were culture positive for pulmonary tuberculosis 3 to 4 years before tuberculosis was diagnosed in the bird. Although humans have not been shown to acquire tuberculosis from birds, an infected bird may be a sentinel for human infection.


2011 ◽  
Vol 50 (1) ◽  
pp. 31-38 ◽  
Author(s):  
Manoj Kumar ◽  
Farrah G. Khan ◽  
Sandeep Sharma ◽  
Rajinder Kumar ◽  
Jaya Faujdar ◽  
...  

1995 ◽  
Vol 63 (8) ◽  
pp. 3231-3234 ◽  
Author(s):  
M Zhang ◽  
Y Lin ◽  
D V Iyer ◽  
J Gong ◽  
J S Abrams ◽  
...  

2021 ◽  
Vol 8 ◽  
Author(s):  
Jason E. Lombard ◽  
Elisabeth A. Patton ◽  
Suzanne N. Gibbons-Burgener ◽  
Rachel F. Klos ◽  
Julie L. Tans-Kersten ◽  
...  

The Mycobacterium tuberculosis complex (MTBC) species includes both M. tuberculosis, the primary cause of human tuberculosis (TB), and M. bovis, the primary cause of bovine tuberculosis (bTB), as well as other closely related Mycobacterium species. Zoonotic transmission of M. bovis from cattle to humans was recognized more than a century ago, but transmission of MTBC species from humans to cattle is less often recognized. Within the last decade, multiple published reports from around the world describe human-to-cattle transmission of MTBC. Three probable cases of human-to-cattle MTBC transmission have occurred in the United States since 2013. In the first case, detection of active TB disease (M. bovis) in a dairy employee in North Dakota prompted testing and ultimate detection of bTB infection in the dairy herd. Whole genome sequencing (WGS) demonstrated a match between the bTB strain in the employee and an infected cow. North Dakota animal and public health officials concluded that the employee's infection was the most likely source of disease introduction in the dairy. The second case involved a Wisconsin dairy herd with an employee diagnosed with TB disease in 2015. Subsequently, the herd was tested twice with no disease detected. Three years later, a cow originating from this herd was detected with bTB at slaughter. The strain in the slaughter case matched that of the past employee based on WGS. The third case was a 4-month-old heifer calf born in New Mexico and transported to Texas. The calf was TB tested per Texas entry requirements and found to have M. tuberculosis. Humans are the suspected source of M. tuberculosis in cattle; however, public health authorities were not able to identify an infected human associated with the cattle operation. These three cases provide strong evidence of human-to-cattle transmission of MTBC organisms and highlight human infection as a potential source of introduction of MTBC into dairy herds in the United States. To better understand and address the issue, a multisectoral One Health approach is needed, where industry, public health, and animal health work together to better understand the epidemiology and identify preventive measures to protect human and animal health.


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