Proteomic characterization of pleural effusion, a specific host niche of Mycoplasma mycoides subsp. mycoides from cattle with contagious bovine pleuropneumonia (CBPP)

Weldearegay, Yenehiwot Berhanu; Pich, Andreas; Schieck, Elise; Liljander, Anne; Gicheru, Nimmo; Wesonga, Hezron; Thiaucourt, François; Kiirika, Leonard Muriithi; Valentin‐Weigand, Peter; Jores, Joerg; Meens, Jochen

doi:10.1016/j.jprot.2015.10.016

Cited by 10 publications

(9 citation statements)

References 72 publications

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“…mycoides (Mmm), a species closely related to Mmc, was analyzed in vitro and in vivo. These studies showed that five of six homologs of MIB and MIP could be detected in Mmm (37) and confirmed that these proteins were located at the surface of the bacteria (38). Based on sequence similarity values, the MIP and MIB homologs expressed in Mmm correspond to the proteins 0582, 0583, 0584, 0587, and 0588 from Mmc.…”

Section: Discussionmentioning

confidence: 55%

MIB–MIP is a mycoplasma system that captures and cleaves immunoglobulin G

Arfi

Minder

Primo

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Mycoplasmas are "minimal" bacteria able to infect humans, wildlife, and a large number of economically important livestock species. Mycoplasma infections include a spectrum of clinical manifestations ranging from simple fever to fulminant inflammatory diseases with high mortality rates. These infections are mostly chronic, suggesting that mycoplasmas have developed means to evade the host immune response. Here we present and functionally characterize a two-protein system from Mycoplasma mycoides subspecies capri that is involved in the capture and cleavage of IgG. The first component, Mycoplasma Ig binding protein (MIB), is an 83-kDa protein that is able to tightly bind to the Fv region of a wide range of IgG. The second component, Mycoplasma Ig protease (MIP), is a 97-kDa serine protease that is able to cleave off the VH domain of IgG. We demonstrate that MIB is necessary for the proteolytic activity of MIP. Cleavage of IgG requires a sequential interaction of the different partners of the system: first MIB captures the IgG, and then MIP is recruited to the MIB-IgG complex, enabling protease activity. MIB and MIP are encoded by two genes organized in tandem, with homologs found in the majority of pathogenic mycoplasmas and often in multiple copies. Phylogenetic studies suggest that genes encoding the MIB-MIP system are specific to mycoplasmas and have been disseminated by horizontal gene transfer. These results highlight an original and complex system targeting the host immunoglobulins, playing a potentially key role in the immunity evasion by mycoplasmas.

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Section: Discussionmentioning

confidence: 55%

MIB–MIP is a mycoplasma system that captures and cleaves immunoglobulin G

Arfi

Minder

Primo

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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“…The MIB-MIP system was shown to be active in vitro , and to be present in large amounts at the cell surface (Krasteva et al, 2014) during infection (Weldearegay et al, 2016). Two animal sera were selected from the in vivo infection trial: CK51 from the GM12 group and CK45 from the GM12::YCpMmyc1.1-Δ 68 group and tested for cleavage of IgG.…”

Section: Resultsmentioning

confidence: 99%

Removal of a Subset of Non-essential Genes Fully Attenuates a Highly Virulent Mycoplasma Strain

Jores

Stolzmann

et al. 2019

Front. Microbiol.

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Mycoplasmas are the smallest free-living organisms and cause a number of economically important diseases affecting humans, animals, insects, and plants. Here, we demonstrate that highly virulent Mycoplasma mycoides subspecies capri ( Mmc ) can be fully attenuated via targeted deletion of non-essential genes encoding, among others, potential virulence traits. Five genomic regions, representing approximately 10% of the original Mmc genome, were successively deleted using Saccharomyces cerevisiae as an engineering platform. Specifically, a total of 68 genes out of the 432 genes verified to be individually non-essential in the JCVI-Syn3.0 minimal cell, were excised from the genome. In vitro characterization showed that this mutant was similar to its parental strain in terms of its doubling time, even though 10% of the genome content were removed. A novel in vivo challenge model in goats revealed that the wild-type parental strain caused marked necrotizing inflammation at the site of inoculation, septicemia and all animals reached endpoint criteria within 6 days after experimental infection. This is in contrast to the mutant strain, which caused no clinical signs nor pathomorphological lesions. These results highlight, for the first time, the rational design, construction and complete attenuation of a Mycoplasma strain via synthetic genomics tools. Trait addition using the yeast-based genome engineering platform and subsequent in vitro or in vivo trials employing the Mycoplasma chassis will allow us to dissect the role of individual candidate Mycoplasma virulence factors and lead the way for the development of an attenuated designer vaccine.

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“…The MIB-MIP system was shown to be active in vitro, and to be present in large amounts at the cell surface (17) during infection (18). Two animal sera were selected from the in vivo infection ‡ trial: CK51 from the GM12 group and CK45 from the GM12::YCpMmyc1.1- ∆68 group and tested for cleavage of IgG.…”

Section: Resultsmentioning

confidence: 99%

Removal of a subset of non-essential genes fully attenuates a highly virulentMycoplasmastrain

Jores

Stolzmann³

et al. 2019

Preprint

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IMPORTANCE 43Members of the Mycoplasma mycoides cluster cause important animal plaques in Africa and 44 Asia, which impact animal welfare, provision of food and the life of thousands of small-scale 45 farmers. We applied synthetic biology tools to Mycoplasma mycoides in order to design and 46 create a fully attenuated Mycoplasma strain that was subsequently confirmed in vivo using a 47 65 pathogenicity. Due to their regressive evolution by gene loss , mycoplasmas appear to lack 66 many of the common bacterial effectors and toxins used to interact with their hosts or to escape 67 the hosts' immune systems (6, 7). Lipoproteins have been proposed to be involved in both 68 aspects by using their cytoadherent properties and allowing antigenic variability through phase 69 or sequence variation (8). Other candidate virulence traits, such as the Mycoplasma Ig binding 70 protein-Mycoplasma Ig protease (MIB-MIP) system (9) and the hydrogen peroxide production 71 system (10) have been suggested, but not confirmed in vivo. 72

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Proteomic characterization of pleural effusion, a specific host niche of Mycoplasma mycoides subsp. mycoides from cattle with contagious bovine pleuropneumonia (CBPP)

Cited by 10 publications

References 72 publications

MIB–MIP is a mycoplasma system that captures and cleaves immunoglobulin G

MIB–MIP is a mycoplasma system that captures and cleaves immunoglobulin G

Removal of a Subset of Non-essential Genes Fully Attenuates a Highly Virulent Mycoplasma Strain

Removal of a subset of non-essential genes fully attenuates a highly virulentMycoplasmastrain

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