Molecular basis for the evolution of species-specific hemoglobin capture by pathogenic Staphylococcus

Molecular Basis for the Evolution of Species-Specific Hemoglobin Capture by Staphylococcus aureus

mBio ◽

10.1128/mbio.01524-18 ◽

2018 ◽

Vol 9 (6) ◽

Cited By ~ 6

Author(s):

Jacob E. Choby ◽

Hanna B. Buechi ◽

Allison J. Farrand ◽

Eric P. Skaar ◽

Matthew F. Barber

Keyword(s):

Staphylococcus Aureus ◽

Pathogenic Bacteria ◽

Rapid Evolution ◽

Invasive Disease ◽

Globin Genes ◽

Content Type ◽

Adaptive Mutations ◽

Bacterial Hemoglobin ◽

Binding Interface ◽

Species Specific

ABSTRACT Metals are a limiting resource for pathogenic bacteria and must be scavenged from host proteins. Hemoglobin provides the most abundant source of iron in the human body and is required by several pathogens to cause invasive disease. However, the consequences of hemoglobin evolution for bacterial nutrient acquisition remain unclear. Here we show that the α- and β-globin genes exhibit strikingly parallel signatures of adaptive evolution across simian primates. Rapidly evolving sites in hemoglobin correspond to binding interfaces of IsdB, a bacterial hemoglobin receptor harbored by pathogenic Staphylococcus aureus. Using an evolution-guided experimental approach, we demonstrate that the divergence between primates and staphylococcal isolates governs hemoglobin recognition and bacterial growth. The reintroduction of putative adaptive mutations in α- or β-globin proteins was sufficient to impair S. aureus binding, providing a mechanism for the evolution of disease resistance. These findings suggest that bacterial hemoprotein capture has driven repeated evolutionary conflicts with hemoglobin during primate descent. IMPORTANCE During infection, bacteria must steal metals, including iron, from the host tissue. Therefore, pathogenic bacteria have evolved metal acquisition systems to overcome the elaborate processes mammals use to withhold metal from pathogens. Staphylococcus aureus uses IsdB, a hemoglobin receptor, to thieve iron-containing heme from hemoglobin within human blood. We find evidence that primate hemoglobin has undergone rapid evolution at protein surfaces contacted by IsdB. Additionally, variation in the hemoglobin sequences among primates, or variation in IsdB of related staphylococci, reduces bacterial hemoglobin capture. Together, these data suggest that S. aureus has evolved to recognize human hemoglobin in the face of rapid evolution at the IsdB binding interface, consistent with repeated evolutionary conflicts in the battle for iron during host-pathogen interactions.

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Species-specific responses of tree saplings to herbivory in contrasting light environments: An experimental approach

Ecoscience ◽

10.2980/17-2-3286 ◽

2010 ◽

Vol 17 (2) ◽

pp. 156-165 ◽

Cited By ~ 11

Author(s):

Elena Baraza ◽

Regino Zamora ◽

José A. Hódar

Keyword(s):

Experimental Approach ◽

Species Specific

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Severe invasive disease caused by hypervirulent Klebsiella pneumoniae: a case report

10.22514/sv.2021.052 ◽

2021 ◽

Keyword(s):

Klebsiella Pneumoniae ◽

Patient Outcomes ◽

Liver Abscess ◽

Pathogenic Bacteria ◽

Treatment Options ◽

Invasive Disease ◽

Multiple Organ ◽

Multiple Organ Dysfunction ◽

Antimicrobial Drugs ◽

Life Threatening

Klebsiella pneumoniae (K. pneumoniae) is a common pathogenic bacteria that causes numerous infectious diseases. Hypervirulent K. pneumoniae (hvKP) can lead to invasive K. pneumoniae liver abscess syndrome, which can induce life-threatening multiple organ dysfunction syndrome or septic shock. We report a case of invasive K. pneumoniae liver abscess syndrome caused by hvKP and discuss the treatment options of this syndrome. Appropriate antimicrobial drugs should be administered to improve prognosis and prevent complications, and laboratory testing is essential to guide clinical management and optimize patient outcomes.

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Antimicrobial Susceptibility Testing and Tentative Epidemiological Cutoff Values for FiveBacillusSpecies Relevant for Use as Animal Feed Additives or for Plant Protection

Applied and Environmental Microbiology ◽

10.1128/aem.01108-18 ◽

2018 ◽

Vol 84 (19) ◽

Cited By ~ 7

Author(s):

Yvonne Agersø ◽

Birgitte Stuer-Lauridsen ◽

Karin Bjerre ◽

Michelle Geervliet Jensen ◽

Eric Johansen ◽

...

Keyword(s):

Antimicrobial Resistance ◽

Resistance Genes ◽

Pathogenic Bacteria ◽

Animal Feed ◽

Bacterial Species ◽

Feed Additives ◽

Content Type ◽

Cutoff Values ◽

Antimicrobial Resistance Genes ◽

Species Specific

ABSTRACTBacillus megaterium(n= 29),Bacillus velezensis(n= 26),Bacillus amyloliquefaciens(n= 6),Bacillus paralicheniformis(n= 28), andBacillus licheniformis(n= 35) strains from different sources, origins, and time periods were tested for the MICs for nine antimicrobial agents by the CLSI-recommended method (Mueller-Hinton broth, 35°C, for 18 to 20 h), as well as with a modified CLSI method (Iso-Sensitest [IST] broth, 37°C [35°C forB. megaterium], 24 h). This allows a proposal of species-specific epidemiological cutoff values (ECOFFs) for the interpretation of antimicrobial resistance in these species. MICs determined by the modified CLSI method were 2- to 16-fold higher than with the CLSI-recommended method for several antimicrobials. The MIC distributions differed between species for five of the nine antimicrobials. Consequently, use of the modified CLSI method and interpretation of resistance by use of species-specific ECOFFs is recommended. The genome sequences of all strains were determined and used for screening for resistance genes against the ResFinder database and for multilocus sequence typing. A putative chloramphenicol acetyltransferase (cat) gene was found in oneB. megateriumstrain with an elevated chloramphenicol MIC compared to the otherB. megateriumstrains. InB. velezensisandB. amyloliquefaciens, a putative tetracycline efflux gene,tet(L), was found in all strains (n= 27) with reduced tetracycline susceptibility but was absent in susceptible strains. AllB. paralicheniformisand 23% ofB. licheniformisstrains had elevated MICs for erythromycin and harboredermD. The presence of these resistance genes follows taxonomy suggesting they may be intrinsic rather than horizontally acquired. Reduced susceptibility to chloramphenicol, streptomycin, and clindamycin could not be explained in all species.IMPORTANCEWhen commercializing bacterial strains, likeBacillusspp., for feed applications or plant bioprotection, it is required that the strains are free of acquired antimicrobial resistance genes that could potentially spread to pathogenic bacteria, thereby adding to the pool of resistance genes that may cause treatment failures in humans or animals. Conversely, if antimicrobial resistance is intrinsic to a bacterial species, the risk of spreading horizontally to other bacteria is considered very low. Reliable susceptibility test methods and interpretation criteria at the species level are needed to accurately assess antimicrobial resistance levels. In the present study, tentative ECOFFs for fiveBacillusspecies were determined, and the results showed that the variation in MICs followed the respective species. Moreover, putative resistance genes, which were detected by whole-genome sequencing and suggested to be intrinsic rather that acquired, could explain the resistance phenotypes in most cases.

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Visualization of Host-Polerovirus Interaction Topologies Using Protein Interaction Reporter Technology

Journal of Virology ◽

10.1128/jvi.01706-15 ◽

2015 ◽

Vol 90 (4) ◽

pp. 1973-1987 ◽

Cited By ~ 25

Author(s):

Stacy L. DeBlasio ◽

Juan D. Chavez ◽

Mariko M. Alexander ◽

John Ramsey ◽

Jimmy K. Eng ◽

...

Keyword(s):

Mass Spectrometry ◽

Protein Interaction ◽

Protein Interactions ◽

Interaction Network ◽

Host Protein ◽

Host Proteins ◽

Content Type ◽

Host Pathogen ◽

Pathogen Protein ◽

Binding Interfaces

ABSTRACTDemonstrating direct interactions between host and virus proteins during infection is a major goal and challenge for the field of virology. Most protein interactions are not binary or easily amenable to structural determination. Using infectious preparations of a polerovirus (Potato leafroll virus[PLRV]) and protein interaction reporter (PIR), a revolutionary technology that couples a mass spectrometric-cleavable chemical cross-linker with high-resolution mass spectrometry, we provide the first report of a host-pathogen protein interaction network that includes data-derived, topological features for every cross-linked site that was identified. We show that PLRV virions have hot spots of protein interaction and multifunctional surface topologies, revealing how these plant viruses maximize their use of binding interfaces. Modeling data, guided by cross-linking constraints, suggest asymmetric packing of the major capsid protein in the virion, which supports previous epitope mapping studies. Protein interaction topologies are conserved with other species in theLuteoviridaeand with unrelated viruses in theHerpesviridaeandAdenoviridae. Functional analysis of three PLRV-interacting host proteinsin plantausing a reverse-genetics approach revealed a complex, molecular tug-of-war between host and virus. Structural mimicry and diversifying selection—hallmarks of host-pathogen interactions—were identified within host and viral binding interfaces predicted by our models. These results illuminate the functional diversity of the PLRV-host protein interaction network and demonstrate the usefulness of PIR technology for precision mapping of functional host-pathogen protein interaction topologies.IMPORTANCEThe exterior shape of a plant virus and its interacting host and insect vector proteins determine whether a virus will be transmitted by an insect or infect a specific host. Gaining this information is difficult and requires years of experimentation. We used protein interaction reporter (PIR) technology to illustrate how viruses exploit host proteins during plant infection. PIR technology enabled our team to precisely describe the sites of functional virus-virus, virus-host, and host-host protein interactions using a mass spectrometry analysis that takes just a few hours. Applications of PIR technology in host-pathogen interactions will enable researchers studying recalcitrant pathogens, such as animal pathogens where host proteins are incorporated directly into the infectious agents, to investigate how proteins interact during infection and transmission as well as develop new tools for interdiction and therapy.

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Functional Relationships between the AcrA Hairpin Tip Region and the TolC Aperture Tip Region for the Formation of the Bacterial Tripartite Efflux Pump AcrAB-TolC

Journal of Bacteriology ◽

10.1128/jb.00334-10 ◽

2010 ◽

Vol 192 (17) ◽

pp. 4498-4503 ◽

Cited By ~ 37

Author(s):

Hong-Man Kim ◽

Yongbin Xu ◽

Minho Lee ◽

Shunfu Piao ◽

Se-Hoon Sim ◽

...

Keyword(s):

Functional Data ◽

Molecular Basis ◽

Pathogenic Bacteria ◽

Essential Role ◽

Efflux Pump ◽

Gram Negative Bacteria ◽

Conserved Residues ◽

Membrane Fusion Protein ◽

Functional Relationships

ABSTRACT Tripartite efflux pumps found in Gram-negative bacteria are involved in antibiotic resistance and toxic-protein secretion. In this study, we show, using site-directed mutational analyses, that the conserved residues located in the tip region of the α-hairpin of the membrane fusion protein (MFP) AcrA play an essential role in the action of the tripartite efflux pump AcrAB-TolC. In addition, we provide in vivo functional data showing that both the length and the amino acid sequence of the α-hairpin of AcrA can be flexible for the formation of a functional AcrAB-TolC pump. Genetic-complementation experiments further indicated functional interrelationships between the AcrA hairpin tip region and the TolC aperture tip region. Our findings may offer a molecular basis for understanding the multidrug resistance of pathogenic bacteria.

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Purification and preliminary characterization of four Rel homologues from pathogenic bacteria: Implications for species-specific inhibitor design

Protein Expression and Purification ◽

10.1016/j.pep.2020.105760 ◽

2021 ◽

Vol 177 ◽

pp. 105760

Author(s):

Vinayak Hegde ◽

Apoorva S. Raman ◽

Pratik Rajendra Patil ◽

Balaji Prakash

Keyword(s):

Pathogenic Bacteria ◽

Specific Inhibitor ◽

Inhibitor Design ◽

Preliminary Characterization ◽

Species Specific

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Molecular Basis of the Ternary Interaction between NS1 of the 1918 Influenza A Virus, PI3K, and CRK

Viruses ◽

10.3390/v12030338 ◽

2020 ◽

Vol 12 (3) ◽

pp. 338

Author(s):

Alyssa Dubrow ◽

Sirong Lin ◽

Nowlan Savage ◽

Qingliang Shen ◽

Jae-Hyun Cho

Keyword(s):

Influenza A Virus ◽

Molecular Basis ◽

Influenza A ◽

Host Protein ◽

Structural Protein ◽

Host Proteins ◽

Ternary Interaction ◽

Important Virulence Factor ◽

1918 Influenza ◽

Phosphoinositide 3 Kinase

The 1918 influenza A virus (IAV) caused the worst flu pandemic in human history. Non-structural protein 1 (NS1) is an important virulence factor of the 1918 IAV and antagonizes host antiviral immune responses. NS1 increases virulence by activating phosphoinositide 3-kinase (PI3K) via binding to the p85β subunit of PI3K. Intriguingly, unlike the NS1 of other human IAV strains, 1918 NS1 hijacks another host protein, CRK, to form a ternary complex with p85β, resulting in hyperactivation of PI3K. However, the molecular basis of the ternary interaction between 1918 NS1, CRK, and PI3K remains elusive. Here, we report the structural and thermodynamic bases of the ternary interaction. We find that the C-terminal tail (CTT) of 1918 NS1 remains highly flexible in the complex with p85β. Thus, the CTT of 1918 NS1 in the complex with PI3K can efficiently hijack CRK. Notably, our study indicates that 1918 NS1 enhances its affinity to p85β in the presence of CRK, which might result in enhanced activation of PI3K. Our results provide structural insight into how 1918 NS1 hijacks two host proteins simultaneously.

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Pediatric Bacterial Meningitis Surveillance in Nigeria From 2010 to 2016, Prior to and During the Phased Introduction of the 10-Valent Pneumococcal Conjugate Vaccine

Clinical Infectious Diseases ◽

10.1093/cid/ciz474 ◽

2019 ◽

Vol 69 (Supplement_2) ◽

pp. S81-S88 ◽

Cited By ~ 2

Author(s):

Beckie N Tagbo ◽

Rowan E Bancroft ◽

Iretiola Fajolu ◽

Mohammed B Abdulkadir ◽

Muhammad F Bashir ◽

...

Keyword(s):

Bacterial Meningitis ◽

Conjugate Vaccine ◽

Pneumococcal Conjugate Vaccine ◽

Invasive Disease ◽

Latex Agglutination ◽

World Health ◽

Vaccine Introduction ◽

Vaccine Type ◽

Health Organization ◽

Species Specific

Abstract Background Historically, Nigeria has experienced large bacterial meningitis outbreaks with high mortality in children. Streptococcus pneumoniae (pneumococcus), Neisseria meningitidis (meningococcus), and Haemophilus influenzae are major causes of this invasive disease. In collaboration with the World Health Organization, we conducted longitudinal surveillance in sentinel hospitals within Nigeria to establish the burden of pediatric bacterial meningitis (PBM). Methods From 2010 to 2016, cerebrospinal fluid was collected from children <5 years of age, admitted to 5 sentinel hospitals in 5 Nigerian states. Microbiological and latex agglutination techniques were performed to detect the presence of pneumococcus, meningococcus, and H. influenzae. Species-specific polymerase chain reaction and serotyping/grouping were conducted to determine specific causative agents of PBM. Results A total of 5134 children with suspected meningitis were enrolled at the participating hospitals; of these 153 (2.9%) were confirmed PBM cases. The mortality rate for those infected was 15.0% (23/153). The dominant pathogen was pneumococcus (46.4%: 71/153) followed by meningococcus (34.6%: 53/153) and H. influenzae (19.0%: 29/153). Nearly half the pneumococcal meningitis cases successfully serotyped (46.4%: 13/28) were caused by serotypes that are included in the 10-valent pneumococcal conjugate vaccine. The most prevalent meningococcal and H. influenzae strains were serogroup W and serotype b, respectively. Conclusions Vaccine-type bacterial meningitis continues to be common among children <5 years in Nigeria. Challenges with vaccine introduction and coverage may explain some of these finding. Continued surveillance is needed to determine the distribution of serotypes/groups of meningeal pathogens across Nigeria and help inform and sustain vaccination policies in the country.

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Structure and function of minor pilins of type IV pili

Medical Microbiology and Immunology ◽

10.1007/s00430-019-00642-5 ◽

2019 ◽

Vol 209 (3) ◽

pp. 301-308 ◽

Cited By ~ 4

Author(s):

Theis Jacobsen ◽

Benjamin Bardiaux ◽

Olivera Francetic ◽

Nadia Izadi-Pruneyre ◽

Michael Nilges

Keyword(s):

Pathogenic Bacteria ◽

Type Iv Pili ◽

Host Cells ◽

Type Ii Secretion ◽

Type Iv Pilus ◽

Type Iv ◽

Flexible Fibers ◽

Multiple Copies ◽

Species Specific ◽

And Function

AbstractType IV pili are versatile and highly flexible fibers formed on the surface of many Gram-negative and Gram-positive bacteria. Virulence and infection rate of several pathogenic bacteria, such as Neisseria meningitidis and Pseudomonas aeruginosa, are strongly dependent on the presence of pili as they facilitate the adhesion of the bacteria to the host cell. Disruption of the interactions between the pili and the host cells by targeting proteins involved in this interaction could, therefore, be a treatment strategy. A type IV pilus is primarily composed of multiple copies of protein subunits called major pilins. Additional proteins, called minor pilins, are present in lower abundance, but are essential for the assembly of the pilus or for its specific functions. One class of minor pilins is required to initiate the formation of pili, and may form a complex similar to that identified in the related type II secretion system. Other, species-specific minor pilins in the type IV pilus system have been shown to promote additional functions such as DNA binding, aggregation and adherence. Here, we will review the structure and the function of the minor pilins from type IV pili.

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