Regulation of fungal extracellular proteases and their role in mammalian pathogenesis

1995 ◽  
Vol 73 (S1) ◽  
pp. 1065-1070 ◽  
Author(s):  
Michael Hensel ◽  
Christoph M. Tang ◽  
Herbert N. Arst Jr. ◽  
David W. Holden
Keyword(s):  
Gene Disruption ◽  
Immunocompromised Host ◽  
Protease Production ◽  
Virulence Determinants ◽  
Firm Conclusion ◽  
Extracellular Proteases ◽  
Wide Domain ◽  
Sequential Inactivation ◽  
Key Words Aspergillus

Fungal infection in the immunocompromised host is a problem of increasing importance. The virulence determinants of Aspergillus fumigatus, the major agent of invasive aspergillosis, and of Candida albicans, causing candidiasis, are not well characterized. For both pathogens, the involvement of extracellular proteases in pathogenesis is discussed. The use of gene disruption techniques to inactivate the A. fumigatus alkaline protease and metalloprotease genes has led to the firm conclusion that neither of these enzymes has a significant role in virulence. The diploid nature of C. albicans (necessitating sequential inactivation of both alleles for gene disruption studies) and the presence of a multigene family encoding secreted aspartyl proteases has hampered progress in understanding the role of proteases in virulence. We discuss the involvement of wide-domain regulators in the control of protease production and give an example of how one of these regulators (encoded by the areA gene) has been used in virulence studies. Key words: Aspergillus, Candida, proteases, gene regulation.

Epidemiology and antimicrobial resistance of Acinetobacter

2018 ◽  
Vol 2 (4) ◽  
pp. 46-59
Author(s):  
A.G. Salmanov ◽  
O.M. Verner ◽  
L.F. Slepova
Keyword(s):  
Antibiotic Resistance ◽  
Laboratory Testing ◽  
Immunocompromised Host ◽  
Clinical Problem ◽  
Healthcare Associated Infections ◽  
Opportunistic Bacteria ◽  
Acinetobacter Spp ◽  
Healthcare Associated ◽  
Major Clinical Problem

Species of the Acinetobacter represent opportunistic bacteria with a growing clinical significance for Healthcare-associated infections (HAIs). In this literature review, we focus on the current role of Acinetobacter in infectious pathology and describe taxonomy, pathogenicity, and antibiotic resistance of these bacteria. Pathogenesis and regulation of virulence factors in Acinetobacter spp. are described in detail. The majority of acinetobacterial infections are associated with A. baumannii and occur predominantly in an immunocompromised host. Usually, acinetobacterial  infections  are characterized by local purulent inflammation; in severe cases, meningitis and sepsis may develop. Antibiotic resistance of Acinetobacter is a major clinical problem; therefore we give special attention to laboratory testing of resistance to antibiotics as well as identification of Acinetobacter.

scholarly journals Coupling of epithelial Na+ and Cl− channels by direct and indirect activation by serine proteases

2012 ◽  
Vol 303 (9) ◽  
pp. C936-C946 ◽  
Author(s):  
Veronika Gondzik ◽  
Wolf Michael Weber ◽  
Mouhamed S. Awayda
Keyword(s):  
Serine Proteases ◽  
Collecting Duct ◽  
Short Circuit ◽  
Short Circuit Current ◽  
Epithelial Cell Line ◽  
Extracellular Proteases ◽  
Direct Role ◽  
Renal Epithelial Cell ◽  
Transport Pathways

The mammalian collecting duct (CD) is continuously exposed to urinary proteases. The CD expresses an epithelial Na+ channel (ENaC) that is activated after cleavage by serine proteases. ENaC also exists at the plasma membrane in the uncleaved form, rendering activation by extracellular proteases an important mechanism for regulating Na+ transport. Many exogenous and a small number of endogenous extracellular serine proteases have been shown to activate the channel. Recently, kallikrein 1 (KLK1) was shown to increase γENaC cleavage in the native CD indicating a possible direct role of this endogenous protease in Na+ homeostasis. To explore this process, we examined the coordinated effect of this protease on Na+ and Cl− transport in a polarized renal epithelial cell line (Madin-Darby canine kidney). We also examined the role of native urinary proteases in this process. Short-circuit current ( Isc) was used to measure transport of these ions. The Isc exhibited an ENaC-dependent Na+ component that was amiloride blockable and a cystic fibrosis transmembrane conductance regulator (CFTR)-dependent Cl− component that was blocked by inhibitor 172. Apical application of trypsin, an exogenous S1 serine protease, activated IENaC but was without effects on ICFTR. Subtilisin an exogenous S8 protease that mimics endogenous furin-type proteases activated both currents. A similar activation was also observed with KLK1 and native rat urinary proteases. Activation with urinary proteases occurred within minutes and at protease concentrations similar to those in the CD indicating physiological significance of this process. ENaC activation was irreversible and mediated by enhanced cleavage of γENaC. The activation of CFTR was indirect and likely dependent on activation of an endogenous apical membrane protease receptor. Collectively, these data demonstrate coordinated stimulation of separate Na+ and Cl− transport pathways in renal epithelia by extracellular luminal proteases. They also indicate that baseline urinary proteolytic activity is sufficient to modify Na+ and Cl− transport in these epithelia.

Role of imaging and interventional techniques in the diagnosis of respiratory disease in the immunocompromised host

1988 ◽  
Vol 3 (2) ◽  
pp. 1-20 ◽  
Author(s):  
Frederick P. Ognibene ◽  
Harvey I. Pass ◽  
Jack A. Roth ◽  
James H. Shelhamer ◽  
Eric N.C. Milne
Keyword(s):  
Respiratory Disease ◽  
Immunocompromised Host ◽  
Interventional Techniques

Bacterial Quorum Sensing During Infection

2020 ◽  
Vol 74 (1) ◽  
pp. 201-219 ◽  
Author(s):  
Sheyda Azimi ◽  
Alexander D. Klementiev ◽  
Marvin Whiteley ◽  
Stephen P. Diggle
Keyword(s):  
Quorum Sensing ◽  
Bacterial Infections ◽  
Pathogenic Bacteria ◽  
Human Infection ◽  
Future Research ◽  
Virulence Determinants ◽  
Plant Laboratory ◽  
Bacterial Quorum Sensing ◽  
Bacterial Quorum

Bacteria are highly interactive and possess an extraordinary repertoire of intercellular communication and social behaviors, including quorum sensing (QS). QS has been studied in detail at the molecular level, so mechanistic details are well understood in many species and are often involved in virulence. The use of different animal host models has demonstrated QS-dependent control of virulence determinants and virulence in several human pathogenic bacteria. QS also controls virulence in several plant pathogenic species. Despite the role QS plays in virulence during animal and plant laboratory-engineered infections, QS mutants are frequently isolated from natural infections, demonstrating that the function of QS during infection and its role in pathogenesis remain poorly understood and are fruitful areas for future research. We discuss the role of QS during infection in various organisms and highlight approaches to better understand QS during human infection. This is an important consideration in an era of growing antimicrobial resistance, when we are looking for new ways to target bacterial infections.

scholarly journals Senescence and Host–Pathogen Interactions

Cells ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 1747 ◽  
Author(s):  
Daniel Humphreys ◽  
Mohamed ElGhazaly ◽  
Teresa Frisan
Keyword(s):  
Chronic Infection ◽  
Virulence Determinants ◽  
Viral Pathogens ◽  
Host Pathogen Interaction ◽  
Cycle Arrest ◽  
Age Related ◽  
Host Pathogen ◽  
Weak Points ◽  
Innate Defence

Damage to our genomes triggers cellular senescence characterised by stable cell cycle arrest and a pro-inflammatory secretome that prevents the unrestricted growth of cells with pathological potential. In this way, senescence can be considered a powerful innate defence against cancer and viral infection. However, damage accumulated during ageing increases the number of senescent cells and this contributes to the chronic inflammation and deregulation of the immune function, which increases susceptibility to infectious disease in ageing organisms. Bacterial and viral pathogens are masters of exploiting weak points to establish infection and cause devastating diseases. This review considers the emerging importance of senescence in the host–pathogen interaction: we discuss the pathogen exploitation of ageing cells and senescence as a novel hijack target of bacterial pathogens that deploys senescence-inducing toxins to promote infection. The persistent induction of senescence by pathogens, mediated directly through virulence determinants or indirectly through inflammation and chronic infection, also contributes to age-related pathologies such as cancer. This review highlights the dichotomous role of senescence in infection: an innate defence that is exploited by pathogens to cause disease.

scholarly journals Role of Ethanolamine Utilization Genes in Host Colonization during Urinary Tract Infection

2017 ◽  
Vol 86 (3) ◽  
Author(s):  
Anna Sintsova ◽  
Sara Smith ◽  
Sargurunathan Subashchandrabose ◽  
Harry L. Mobley
Keyword(s):  
Urinary Tract Infection ◽  
Urinary Tract ◽  
Tract Infection ◽  
Mouse Model ◽  
Virulence Determinants ◽  
Content Type ◽  
Immunocompromised Mouse ◽  
Common Infection ◽  
Increased Susceptibility

ABSTRACTUrinary tract infection (UTI) is the second most common infection in humans, making it a global health priority. Nearly half of all women will experience a symptomatic UTI, with uropathogenicEscherichia coli(UPEC) being the major causative agent of the infection. Although there has been extensive research on UPEC virulence determinants, the importance of host-specific metabolism remains understudied. We report here that UPEC upregulates the expression of ethanolamine utilization genes during uncomplicated UTIs in humans. We further show that UPEC ethanolamine metabolism is required for effective bladder colonization in the mouse model of ascending UTI and is dispensable for bladder colonization in an immunocompromised mouse model of UTI. We demonstrate that although ethanolamine metabolism mutants do not show increased susceptibility to antimicrobial responses of neutrophils, this metabolic pathway is important for surviving the innate immune system during UTI. This study reveals a novel aspect of UPEC metabolism in the host and provides evidence for an underappreciated link between bacterial metabolism and the host immune response.

Extracellular Heat-Resistant Proteases of Psychrotrophic Pseudomonads

1983 ◽  
Vol 46 (2) ◽  
pp. 90-94 ◽  
Author(s):  
THAKOR R. PATEL ◽  
FRANCIS M. BARTLETT ◽  
JAWED HAMID
Keyword(s):  
Protease Activity ◽  
Milk Powder ◽  
Milk Proteins ◽  
Raw Milk ◽  
Enzyme Synthesis ◽  
Maximum Activity ◽  
Protease Production ◽  
Divalent Metal Ions ◽  
Extracellular Proteases ◽  
Heat Resistant

Several bacterial isolates from raw milk produced proteases. Most of such 28 isolates were gram-negative rods which were oxidase- and catalase-positive. All the isolates grew at temperatures in the range of 0–35°C, but failed to grow at 37°C. Nineteen of these isolates were tentatively assigned to genus Pseudomonas, and were used in the present investigation. Extracellular proteases from these psychrotrophic pseudomonads were heat-resistant, being able to retain partial activity even after heat-treatment at 120°C for 10 min. Milk proteins were preferred substrates by these proteases although some also hydrolysed bovine serum albumin, hemoglobin and ovalbumin. The optimum pH for the maximum activity was between pH 7.2 and 7.4. Divalent metal ions like Cu2+, Co2+, Hg2+, and Zn2+ were inhibitory to protease activity while Ca2+, Mg2+, and Mn2+ had little or no inhibitory effect on the proteases. Induced levels of protease production were observed when cultures were grown in minimal media containing either casein or nonfat dried milk powder. Glucose, citrate and lactose repressed enzyme synthesis in a minmal salts medium containing either casein or nonfat dried milk powder. Protease activity was also detected in cultures grown in minimal medium containing glutamine. Proteases from different isolates varied in their molecular weights.

scholarly journals Reversible Regulation of Polyubiquitin Gene UBC via Modified Inducible CRISPR/Cas9 System

2019 ◽  
Vol 20 (13) ◽  
pp. 3168 ◽  
Author(s):  
Seung-Woo Han ◽  
Byung-Kwon Jung ◽  
So-Hyun Park ◽  
Kwon-Yul Ryu
Keyword(s):  
Fusion Protein ◽  
Stress Resistance ◽  
Gene Disruption ◽  
Stress Conditions ◽  
Biological Research ◽  
Guide Rna ◽  
Cellular Processes ◽  
Polyubiquitin Gene ◽  
Cellular Machinery

Ubiquitin is required under both normal and stress conditions. Under stress conditions, upregulation of the polyubiquitin gene UBC is essential to meet the requirement of increased ubiquitin levels to confer stress resistance. However, UBC upregulation is usually observed only under stress conditions and not under normal conditions. Therefore, it has not been possible to upregulate UBC under normal conditions to study the effect of excess ubiquitin on cellular machinery. Recently, the CRISPR/Cas9 system has been widely used in biological research as a useful tool to study gene disruption effects. In this study, using an inducible CRISPR/Cas9 variant, a dCas9–VP64 fusion protein, combined with a single guide RNA (sgRNA) containing MS2 aptamer loops and MS2-p65-HSF1, we developed a system to increase the ubiquitin pool via upregulation of UBC. Although it is challenging to upregulate the expression of a gene that is already expressed at high levels, the significance of our system is that UBC upregulation can be induced in an efficient, reversible manner that is compatible with cellular processes, even under normal conditions. This system can be used to study ubiquitin pool dynamics and it will be a useful tool in identifying the role of ubiquitin under normal and stress conditions.

scholarly journals Enhancement of Secretion and Extracellular Stability of Staphylokinase in Bacillus subtilis bywprA Gene Disruption

2000 ◽  
Vol 66 (2) ◽  
pp. 476-480 ◽  
Author(s):  
Sang Jun Lee ◽  
Dong Min Kim ◽  
Kwang Hee Bae ◽  
Si Myung Byun ◽  
Jae Hoon Chung
Keyword(s):  
Bacillus Subtilis ◽  
Gene Disruption ◽  
Therapeutic Potential ◽  
Signal Sequence ◽  
Open Reading Frame ◽  
Expression Plasmid ◽  
Reading Frame ◽  
Extracellular Milieu ◽  
Foreign Proteins

ABSTRACT Staphylokinase (SAK), a polypeptide secreted byStaphylococcus aureus, is a plasminogen activator with a therapeutic potential in thrombosis diseases. A Bacillus subtilis strain which is multiply deficient in exoproteases was transformed by an expression plasmid carrying a promoter and a signal sequence of subtilisin fused in frame with the sak open reading frame. However, the amount of SAK secretion was marginal (45 mg/liter). In contrast, disruption of the wprA gene, which encodes a subtilisin-type protease, strongly promoted the production of SAK in the stationary phase (181 mg/liter). In addition, the extracellular stability of mature SAK was dramatically enhanced. These data indicate a significant role of the wprA gene product in degrading foreign proteins, both during secretion and in the extracellular milieu.

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