Bacterial Plasminogen Receptors: Mediators of a Multifaceted Relationship

Flores

2016

Microbiol Mol Biol Rev

SUMMARYMoonlighting proteins are multifunctional proteins that participate in unrelated biological processes and that are not the result of gene fusion. A certain number of these proteins have been characterized in yeasts, and the easy genetic manipulation of these microorganisms has been useful for a thorough analysis of some cases of moonlighting. As the awareness of the moonlighting phenomenon has increased, a growing number of these proteins are being uncovered. In this review, we present a crop of newly identified moonlighting proteins from yeasts and discuss the experimental evidence that qualifies them to be classified as such. The variety of moonlighting functions encompassed by the proteins considered extends from control of transcription to DNA repair or binding to plasminogen. We also discuss several questions pertaining to the moonlighting condition in general. The cases presented show that yeasts are important organisms to be used as tools to understand different aspects of moonlighting proteins.

Section: Enzymes Binding Plasminogenmentioning

confidence: 98%

The Expanding Landscape of Moonlighting Proteins in Yeasts

Flores

2016

Microbiol Mol Biol Rev

“…Plasminogen is found in plasma and extracellular fluids, and upon activation is converted to plasmin, which degrades the extracellular matrix and may upregulate matrix metalloproteinases that degrade tight junctions (268). In vitro, plasminogen binds to streptococcal glyceraldehyde-3-phosphate dehydrogenase (269)(270)(271).…”

Section: H Influenzae Quagliarello Et Al First Demonstrated That Hmentioning

confidence: 99%

Pathogens Penetrating the Central Nervous System: Infection Pathways and the Cellular and Molecular Mechanisms of Invasion

et al. 2014

SUMMARY The brain is well protected against microbial invasion by cellular barriers, such as the blood-brain barrier (BBB) and the blood-cerebrospinal fluid barrier (BCSFB). In addition, cells within the central nervous system (CNS) are capable of producing an immune response against invading pathogens. Nonetheless, a range of pathogenic microbes make their way to the CNS, and the resulting infections can cause significant morbidity and mortality. Bacteria, amoebae, fungi, and viruses are capable of CNS invasion, with the latter using axonal transport as a common route of infection. In this review, we compare the mechanisms by which bacterial pathogens reach the CNS and infect the brain. In particular, we focus on recent data regarding mechanisms of bacterial translocation from the nasal mucosa to the brain, which represents a little explored pathway of bacterial invasion but has been proposed as being particularly important in explaining how infection with Burkholderia pseudomallei can result in melioidosis encephalomyelitis.

“…Respiratory pathogens, including Streptococcus pneumoniae, Mycobacterium tuberculosis, Streptococcus pyogenes, Staphylococcus aureus, Neisseria meningitidis, H. influenzae, and Mycoplasma pneumoniae, are known for hijacking plasminogen from the host (31). Bacterial plasminogen surface receptors have diverse structures and functions.…”

Section: Figmentioning

confidence: 99%

Moraxella catarrhalis Binds Plasminogen To Evade Host Innate Immunity

et al. 2015

bSeveral bacterial species recruit the complement regulators C4b-binding protein, factor H, and vitronectin, resulting in resistance against the bactericidal activity of human serum. It was recently demonstrated that bacteria also bind plasminogen, which is converted to plasmin that degrades C3b and C5. In this study, we found that a series of clinical isolates (n ‫؍‬ 58) of the respiratory pathogen Moraxella catarrhalis, which is commonly isolated from preschool children and adults with chronic obstructive pulmonary disease (COPD), significantly binds human plasminogen. Ubiquitous surface protein A2 (UspA2) and hybrid UspA2 (UspA2H) were identified as the plasminogen-binding factors in the outer membrane proteome of Moraxella. Furthermore, expression of a series of truncated recombinant UspA2 and UspA2H proteins followed by a detailed analysis of protein-protein interactions suggested that the N-terminal head domains bound to the kringle domains of plasminogen. The binding affinity constant (K D ) values of full-length UspA2 30 -539 (amino acids 30 to 539 of UspA2) and full-length UspA2H 50 -720 for immobilized plasminogen were 4.8 ؋ 10 ؊8 M and 3.13 ؋ 10 ؊8 M, respectively, as measured by biolayer interferometry. Plasminogen bound to intact M. catarrhalis or to recombinant UspA2/UspA2H was readily accessible for a urokinase plasminogen activator that converted the zymogen into active plasmin, as verified by the specific substrate S-2251 and a degradation assay with fibrinogen. Importantly, plasmin bound at the bacterial surface also degraded C3b and C5, which consequently may contribute to reduced bacterial killing. Our findings suggest that binding of plasminogen to M. catarrhalis may lead to increased virulence and, hence, more efficient colonization of the host.