scholarly journals Evolution of host-microbe cell adherence by receptor domain shuffling

2021 ◽  
Author(s):  
EmilyClare P. Baker ◽  
Ryan Sayegh ◽  
Kristin M. Kohler ◽  
Wyatt Borman ◽  
Claire K. Goodfellow ◽  
...  

Stable adherence to epithelial surfaces is required for colonization by diverse host-associated microbes. Successful attachment of pathogenic microbes via surface adhesin molecules is also the first step in many devastating infections. Despite the primacy of epithelial adherence in establishing host-microbe associations, the evolutionary processes that shape this crucial interface remain enigmatic. Carcinoembryonic antigen associated cell adhesion molecules (CEACAMs) encompass a multifunctional family of vertebrate cell surface proteins which are recurrent targets of bacterial surface adhesins at epithelial surfaces. Here we show that multiple members of the primate CEACAM family exhibit evidence of repeated natural selection at protein surfaces targeted by bacteria, consistent with pathogen-driven evolution. Inter-species diversity of CEACAM proteins, between even closely-related great apes, determines molecular interactions with a range of bacterial adhesins. Phylogenetic analyses reveal that repeated gene conversion of CEACAM extracellular domains during primate divergence plays a key role in limiting bacterial adhesin tropism. Moreover, we demonstrate that gene conversion has continued to shape CEACAM diversity within human populations, with abundant CEACAM1 variants mediating evasion of adhesins from Neisseria gonorrhoeae, the causative agent of gonorrhea. Together this work reveals a mechanism by which gene conversion shapes first contact between microbes and animal hosts.

2019 ◽  
Author(s):  
Bernardo Gutierrez ◽  
Emma Wise ◽  
Steven Pullan ◽  
Christopher Logue ◽  
Thomas A. Bowden ◽  
...  

AbstractThe Amazon basin is host to numerous arthropod-borne viral pathogens that cause febrile disease in humans. Among these,Oropouche orthobunyavirus(OROV) is a relatively understudied member of the Peribunyavirales that causes periodic outbreaks in human populations in Brazil and other South American countries. Although several studies have described the genetic diversity of the virus, the evolutionary processes that shape the viral genome remain poorly understood. Here we present a comprehensive study of the genomic dynamics of OROV that encompasses phylogenetic analysis, evolutionary rate estimates, inference of natural selective pressures, recombination and reassortment, and structural analysis of OROV variants. Our study includes all available published sequences, as well as a set of new OROV genomes sequences obtained from patients in Ecuador, representing the first set of viral genomes from this country. Our results show that differing evolutionary processes on the three segments that encompass the viral genome lead to variable evolutionary rates and TMRCAs that could be explained by cryptic reassortment. We also present the discovery of previously unobserved putative N-linked glycosylation sites, and codons which evolve under positive selection on the viral surface proteins, and discuss the potential role of these features in the evolution of the virus through a combined phylogenetic and structural approach.


2019 ◽  
Vol 2 (1) ◽  
Author(s):  
Benjamin J. Ravenhill ◽  
Usheer Kanjee ◽  
Ambroise Ahouidi ◽  
Luis Nobre ◽  
James Williamson ◽  
...  

Abstract Red blood cells (RBCs) play a critical role in oxygen transport, and are the focus of important diseases including malaria and the haemoglobinopathies. Proteins at the RBC surface can determine susceptibility to disease, however previous studies classifying the RBC proteome have not used specific strategies directed at enriching cell surface proteins. Furthermore, there has been no systematic analysis of variation in abundance of RBC surface proteins between genetically disparate human populations. These questions are important to inform not only basic RBC biology but additionally to identify novel candidate receptors for malarial parasites. Here, we use ‘plasma membrane profiling’ and tandem mass tag-based mass spectrometry to enrich and quantify primary RBC cell surface proteins from two sets of nine donors from the UK or Senegal. We define a RBC surface proteome and identify potential Plasmodium receptors based on either diminished protein abundance, or increased variation in RBCs from West African individuals.


2007 ◽  
Vol 98 (09) ◽  
pp. 488-496 ◽  
Author(s):  
Patric Nitsche-Schmitz ◽  
Manfred Rohde ◽  
Gursharan Chhatwal

SummaryGram-positive cocci are important human pathogens. Streptococci and staphylococci in particular are a major threat to human health,since they cause a variety of serious invasive infections. Their invasion into normally sterile sites of the host depends on elaborated bacterial mechanisms that involve adhesion to the host tissue, its degradation, internalisation by host cells, and passage through epithelia and endothelia. Interactions of bacterial surface proteins with proteins of the host’s extracellular matrix as well as with cell surface receptors are crucial factors in these processes, and some of the key mechanisms are similar in many pathogenic Gram-positive cocci.Therapies that interfere with these mechanisms may become efficient alternatives to today’s antibiotic treatments.


Pathogens ◽  
2018 ◽  
Vol 7 (2) ◽  
pp. 52 ◽  
Author(s):  
Nicole Lamond ◽  
Nancy Freitag

Protection of the developing fetus from pathogens is one of the many critical roles of the placenta. Listeria monocytogenes is one of a select number of pathogens that can cross the placental barrier and cause significant harm to the fetus, leading to spontaneous abortion, stillbirth, preterm labor, and disseminated neonate infection despite antibiotic treatment. Such severe outcomes serve to highlight the importance of understanding how L. monocytogenes mediates infiltration of the placental barrier. Here, we review what is currently known regarding vertical transmission of L. monocytogenes as a result of cell culture and animal models of infection. In vitro cell culture and organ models have been useful for the identification of L. monocytogenes virulence factors that contribute to placental invasion. Examples include members of the Internalin family of bacterial surface proteins such as Interalin (Inl)A, InlB, and InlP that promote invasion of cells at the maternal-fetal interface. A number of animal models have been used to interrogate L. monocytogenes vertical transmission, including mice, guinea pigs, gerbils, and non-human primates; each of these models has advantages while still not providing a comprehensive understanding of L. monocytogenes invasion of the human placenta and/or fetus. These models do, however, allow for the molecular investigation of the balance between fetal tolerance and immune protection from L. monocytogenes during pregnancy.


2010 ◽  
Vol 78 (11) ◽  
pp. 4882-4894 ◽  
Author(s):  
Praveen Alamuri ◽  
Martin Löwer ◽  
Jan A. Hiss ◽  
Stephanie D. Himpsl ◽  
Gisbert Schneider ◽  
...  

ABSTRACT Fimbriae of the human uropathogen Proteus mirabilis are the only characterized surface proteins that contribute to its virulence by mediating adhesion and invasion of the uroepithelia. PMI2122 (AipA) and PMI2575 (TaaP) are annotated in the genome of strain HI4320 as trimeric autotransporters with “adhesin-like” and “agglutinating adhesin-like” properties, respectively. The C-terminal 62 amino acids (aa) in AipA and 76 aa in TaaP are homologous to the translocator domains of YadA from Yersinia enterocolitica and Hia from Haemophilus influenzae. Comparative protein modeling using the Hia three-dimensional structure as a template predicted that each of these domains would contain four antiparallel beta sheets and that they formed homotrimers. Recombinant AipA and TaaP were seen as ∼28 kDa and ∼78 kDa, respectively, in Escherichia coli, and each also formed high-molecular-weight homotrimers, thus supporting this model. E. coli synthesizing AipA or TaaP bound to extracellular matrix proteins with a 10- to 60-fold-higher level of affinity than the control strain. Inactivation of aipA in P. mirabilis strains significantly (P < 0.01) reduced the mutants' ability to adhere to or invade HEK293 cell monolayers, and the functions were restored upon complementation. A 51-aa-long invasin region in the AipA passenger domain was required for this function. E. coli expressing TaaP mediated autoagglutination, and a taaP mutant of P. mirabilis showed significantly (P < 0.05) more reduced aggregation than HI4320. Gly-247 in AipA and Gly-708 in TaaP were indispensable for trimerization and activity. AipA and TaaP individually offered advantages to P. mirabilis in a murine model. This is the first report characterizing trimeric autotransporters in P. mirabilis as afimbrial surface adhesins and autoagglutinins.


2000 ◽  
Vol 46 (2) ◽  
pp. 95-100 ◽  
Author(s):  
Barry Ziola ◽  
Lori Gee ◽  
Nancy N Berg ◽  
Sun Y Lee

Megasphaera cerevisiae is a Gram-negative obligate anaerobe that causes turbidity and off-flavour and aroma in beer. Seven isolates of M. cerevisiae were obtained worldwide, and their extractable surface antigens were focused upon to determine if there is more than one serogroup of this bacterium. Sodium dodecyl sulphate polyacrylamide gel electrophoresis of ethylenediaminetetraacetic acid (EDTA) bacterial extracts revealed a predominant protein with apparent molecular weights of 46 000, 45 000, and 43 000 for three, two, and two isolates, respectively. When mouse antiserum generated against any of the EDTA extracts was reacted with denatured bacterial proteins in immunoblots, all bacterial isolates exhibited extensive cross-reactivity involving three antigens, one being the major EDTA-extractable protein. In contrast, when the sera were tested for surface reactivity with intact bacteria, three cross-reactivity groups were observed, with the groups individually comprised of bacteria having the same size major EDTA-extractable surface protein. When BALB/c mice immunized with a bacterium from each of the three serogroups were used for monoclonal antibody (Mab) hybridoma production, bacterial surface-reactive Mabs were obtained whose reactivities parallel the three polyclonal antibody-defined serogroups. Through combining these surface-reactive Mabs, it will be possible to rapidly detect and identify beer contamination by M. cerevisiae belonging to any serogroup. Key words: beer spoilage bacteria, Megasphaera cerevisiae, monoclonal antibodies, surface proteins, serogroups.


2002 ◽  
Vol 184 (22) ◽  
pp. 6376-6383 ◽  
Author(s):  
Thomas Areschoug ◽  
Sara Linse ◽  
Margaretha Stålhammar-Carlemalm ◽  
Lars-Olof Hedén ◽  
Gunnar Lindahl

ABSTRACT Proline-rich regions have been identified in many surface proteins of pathogenic streptococci and staphylococci. These regions have been suggested to be located in cell wall-spanning domains and/or to be required for surface expression of the protein. Because little is known about these regions, which are found in extensively studied and biologically important surface proteins, we characterized the proline-rich region in one such protein, the β protein of group B streptococci. The proline-rich region in β, designated the XPZ region, has a proline at every third position, and the sequence is highly periodic in other respects. Immunochemical analysis showed that the XPZ region was not associated with the cell wall but was exposed on the bacterial surface. Moreover, characterization of a β mutant lacking the XPZ region demonstrated that this region was not required for surface expression of the β protein. Comparison of the XPZ region in different β proteins showed that it varied in size but always retained the typical sequence periodicity. Circular dichroism spectroscopy indicated that the XPZ region had the structure of a polyproline II helix, an extended and solvent-exposed structure with exactly three residues per turn. Because of the three-residue sequence periodicity in the XPZ region, it is expected to be amphipathic and to have distinct nonpolar and polar surfaces. This study identified a proline-rich structure with unique properties that is exposed on the surface of an important human pathogen.


2020 ◽  
Author(s):  
Chendan Wei ◽  
Zhenyi Wang ◽  
Jianyu Wang ◽  
Jia Teng ◽  
Shaoqi Shen ◽  
...  

AbstractExtensive sequence similarity between duplicated gene pairs produced by paleo-polyploidization may result from illegitimate recombination between homologous chromosomes. The genomes of Asian cultivated rice Xian/indica (XI) and Geng/japonica (GJ) have recently been updated, providing new opportunities for investigating on-going gene conversion events. Using comparative genomics and phylogenetic analyses, we evaluated gene conversion rates between duplicated genes produced by polyploidization 100 million years ago (mya) in GJ and XI. At least 5.19%–5.77% of genes duplicated across three genomes were affected by whole-gene conversion after the divergence of GJ and XI at ~0.4 mya, with more (7.77%–9.53%) showing conversion of only gene portions. Independently converted duplicates surviving in genomes of different subspecies often used the same donor genes. On-going gene conversion frequency was higher near chromosome termini, with a single pair of homoeologous chromosomes 11 and 12 in each genome most affected. Notably, on-going gene conversion has maintained similarity between very ancient duplicates, provided opportunities for further gene conversion, and accelerated rice divergence. Chromosome rearrangement after polyploidization may result in gene loss, providing a basis for on-going gene conversion, and may have contributed directly to restricted recombination/conversion between homoeologous regions. Gene conversion affected biological functions associated with multiple genes, such as catalytic activity, implying opportunities for interaction among members of large gene families, such as NBS-LRR disease-resistance genes, resulting in gene conversion. Duplicated genes in rice subspecies generated by grass polyploidization ~100 mya remain affected by gene conversion at high frequency, with important implications for the divergence of rice subspecies.One-sentence summaryOn-going gene conversion between duplicated genes produced by 100 mya polyploidization contributes to rice subspecies divergence, often involving the same donor genes at chromosome termini.


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