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Fulltext Conflict of interest and signal interference lead to the breakdown of honest signaling

Popat R, Pollitt EJ, Harrison F, Naghra H, Hong KW, Chan KG, et al.

Evolution, 2015 Sep;69(9):2371-83.
PMID: 26282874 DOI: 10.1111/evo.12751

Animals use signals to coordinate a wide range of behaviors, from feeding offspring to predator avoidance. This poses an evolutionary problem, because individuals could potentially signal dishonestly to coerce others into behaving in ways that benefit the signaler. Theory suggests that honest signaling is favored when individuals share a common interest and signals carry reliable information. Here, we exploit the opportunities offered by bacterial signaling to test these predictions with an experimental evolution approach. We show that: (1) reduced relatedness leads to the relative breakdown of signaling, (2) signaling breaks down by the invasion of mutants that show both reduced signaling and reduced response to signal, (3) the genetic route to signaling breakdown is variable, and (4) the addition of artificial signal, to interfere with signal information, also leads to reduced signaling. Our results provide clear support for signaling theory, but we did not find evidence for previously predicted coercion at intermediate relatedness, suggesting that mechanistic details can alter the qualitative nature of specific predictions. Furthermore, populations evolved under low relatedness caused less mortality to insect hosts, showing how signal evolution in bacterial pathogens can drive the evolution of virulence in the opposite direction to that often predicted by theory.

Matched MeSH terms: Virulence
Extracellular BSA-degrading SAPs in the rare pathogen Meyerozyma guilliermondii strain SO as potential virulence factors in candidiasis

Lim SJ, Noor NDM, Sabri S, Ali MSM, Salleh AB, Oslan SN

Microb Pathog, 2024 Aug;193:106773.
PMID: 38960213 DOI: 10.1016/j.micpath.2024.106773

Meyerozyma guilliermondii (Candida guilliermondii) is one of the Candida species associated with invasive candidiasis. With the potential for expressing industrially important enzymes, M. guilliermondii strain SO possessed 99 % proteome similarity with the clinical ATCC 6260 isolate and showed pathogenicity towards zebrafish embryos. Recently, three secreted aspartyl proteinases (SAPs) were computationally identified as potential virulence factors in this strain without in vitro verification of SAP activity. The quantification of Candida SAPs activity in liquid broth were also scarcely reported. Thus, this study aimed to characterize M. guilliermondii strain SO's ability to produce SAPs (MgSAPs) in different conditions (morphology and medium) besides analyzing its growth profile. MgSAPs' capability to cleave bovine serum albumin (BSA) was also determined to propose that MgSAPs as the potential virulence factors compared to the avirulent Saccharomyces cerevisiae. M. guilliermondii strain SO produced more SAPs (higher activity) in yeast nitrogen base-BSA-dextrose broth compared to yeast extract-BSA-dextrose broth despite insignificantly different SAP activity in both planktonic and biofilm cells. FeCl3 supplementation significantly increased the specific protein activity (∼40 %). The BSA cleavage by MgSAPs at an acidic pH was proven through semi-quantitative SDS-PAGE, sharing similar profile with HIV-1 retropepsin. The presented work highlighted the MgSAPs on fungal cell wall and extracellular milieu during host infection could be corroborated to the quantitative production in different growth modes presented herein besides shedding lights on the potential usage of retropepsin's inhibitors in treating candidiasis. Molecular and expression analyses of MgSAPs and their deletion should be further explored to attribute their respective virulence effects.

Matched MeSH terms: Virulence
Humoral immune consequences of Staphylococcus aureus ST239-associated bacteremia

Ghasemzadeh-Moghaddam H, van Wamel W, van Belkum A, Hamat RA, Tavakol M, Neela VK

Eur J Clin Microbiol Infect Dis, 2018 Feb;37(2):255-263.
PMID: 29103153 DOI: 10.1007/s10096-017-3124-3

The humoral immune responses against 46 different staphylococcal antigens in 27 bacteremia patients infected by clonally related methicillin-resistant Staphylococcus aureus (MRSA) strains of a single sequence type (ST) 239 were investigated. A group of non-infected patients (n = 31) hospitalized for different reasons served as controls. All strains were confirmed as ST 239 by S. aureus and mecA-specific PCR, spa, and multi-locus sequence typing (MLST). In each bacteremia patient, a unique pattern of S. aureus antigen-specific immune responses after infection was observed. Antibody levels among bacteremia patients were significantly higher than controls for HlgB (P = 0.001), LukD (P = 0.009), LukF (P = 0.0001), SEA (P = 0.0001), SEB (P = 0.011), SEC (P = 0.010), SEQ (P = 0.049), IsaA (P = 0.043), IsdA (P = 0.038), IsdH (P = 0.01), SdrD (P = 0.001), SdrE (P = 0.046), EsxA (P = 0.0001), and SA0104 (P = 0.0001). On the other hand, the antibody levels were significantly higher among controls for SSL3 (P = 0.009), SSL9 (P = 0.002), and SSL10 (P = 0.007) when the IgG level on the day of infection was compared with that measured on the day of admission. Diversity was observed in the immune response against the antigens. However, a set of antigens (IsaA, IsdA, IsdH, SdrD, and HlgB) triggered a similar type of immune response in different individuals. We suggest that these antigens could be considered when developing a multi-component (passive) vaccine. SEA and/or its specific antibodies seem to play a critical role during ST239 MRSA bacteremia and SEA-targeted therapy may be a strategy to be considered.

Matched MeSH terms: Virulence Factors/immunology
Fulltext Predominance of ST22-MRSA-IV Clone and Emergence of Clones for Methicillin-Resistant Staphylococcus aureus Clinical Isolates Collected from a Tertiary Teaching Hospital Over a Two-Year Period

Niek WK, Teh CSJ, Idris N, Thong KL, Ponnampalavanar S

Jpn J Infect Dis, 2019 Jul 24;72(4):228-236.
PMID: 30814457 DOI: 10.7883/yoken.JJID.2018.289

Methicillin-resistant Staphylococcus aureus (MRSA) is one of the most common nosocomial pathogens, causing mild to severe infections. This study aimed to determine the genotypic and phenotypic characteristics of clinical MRSA isolates collected from a teaching hospital from 2014 - 2015. These isolates were genotyped by multilocus sequence typing, staphylococcal cassette chromosomal mec (SCCmec) typing, virulence genes detection, and pulsed-field gel electrophoresis; they were phenotyped based on their antibiotics susceptibility profiles. The most prevalent sequence type was ST22. ST3547 was identified from a blood isolate from 2015. Three SCCmec types (III in 26.26%, IV in 70.71%, and V in 3.03% isolates) were detected. Agr type I, II, and III were also detected among the isolates. The most prevalent virulence genes found were hemolysin (100%) and intracellular adhesion (91.9%). At least one staphylococcal enterotoxin was detected in 83 (83.8%) isolates. All the isolates were susceptible to vancomycin (minimum inhibitory concentration ≤ 2 μg/mL). Statistical analysis revealed a significant increase in hypertension (p = 0.035), dyslipidemia and obesity (p = 0.046), and previous exposure to any quinolone (p = 0.010) cases over the two-year period. The emergence and circulation of community-associated MRSA variants were observed in our hospital.

Matched MeSH terms: Virulence Factors/genetics
Fulltext Development of live attenuated Enterovirus 71 vaccine strains that confer protection against lethal challenge in mice

Yee PTI, Tan SH, Ong KC, Tan KO, Wong KT, Hassan SS, et al.

Sci Rep, 2019 03 18;9(1):4805.
PMID: 30886246 DOI: 10.1038/s41598-019-41285-z

Besides causing mild hand, foot and mouth infections, Enterovirus A71 (EV-A71) is associated with neurological complications and fatality. With concerns about rising EV-A71 virulence, there is an urgency for more effective vaccines. The live attenuated vaccine (LAV) is a more valuable vaccine as it can elicit both humoral and cellular immune responses. A miRNA-based vaccine strain (pIY) carrying let-7a and miR-124a target genes in the EV-A71 genome which has a partial deletion in the 5'NTR (∆11 bp) and G64R mutation (3Dp°l) was designed. The viral RNA copy number and viral titers of the pIY strain were significantly lower in SHSY-5Y cells that expressed both let-7a and miR-124a. Inhibition of the cognate miRNAs expressed in RD and SHSY-5Y cells demonstrated de-repression of viral mRNA translation. A previously constructed multiply mutated strain, MMS and the pIY vaccine strain were assessed in their ability to protect 4-week old mice from hind limb paralysis. The MMS showed higher amounts of IFN-γ ex vivo than the pIY vaccine strain. There was absence of EV-A71 antigen in the skeletal muscles and spinal cord micrographs of mice vaccinated with the MMS and pIY strains. The MMS and pIY strains are promising LAV candidates developed against severe EV-A71 infections.

Matched MeSH terms: Virulence/genetics*
Fulltext Delineating the Plausible Molecular Vaccine Candidates and Drug Targets of Multidrug-Resistant Acinetobacter baumannii

Mujawar S, Mishra R, Pawar S, Gatherer D, Lahiri C

Front Cell Infect Microbiol, 2019;9:203.
PMID: 31281799 DOI: 10.3389/fcimb.2019.00203

Nosocomial infections have become alarming with the increase of multidrug-resistant bacterial strains of Acinetobacter baumannii. Being the causative agent in ~80% of the cases, these pathogenic gram-negative species could be deadly for hospitalized patients, especially in intensive care units utilizing ventilators, urinary catheters, and nasogastric tubes. Primarily infecting an immuno-compromised system, they are resistant to most antibiotics and are the root cause of various types of opportunistic infections including but not limited to septicemia, endocarditis, meningitis, pneumonia, skin, and wound sepsis and even urinary tract infections. Conventional experimental methods including typing, computational methods encompassing comparative genomics, and combined methods of reverse vaccinology and proteomics had been proposed to differentiate and develop vaccines and/or drugs for several outbreak strains. However, identifying proteins suitable enough to be posed as drug targets and/or molecular vaccines against the multidrug-resistant pathogenic bacterial strains has probably remained an open issue to address. In these cases of novel protein identification, the targets either are uncharacterized or have been unable to confer the most coveted protection either in the form of molecular vaccine candidates or as drug targets. Here, we report a strategic approach with the 3,766 proteins from the whole genome of A. baumannii ATCC19606 (AB) to rationally identify plausible candidates and propose them as future molecular vaccine candidates and/or drug targets. Essentially, we started with mapping the vaccine candidates (VaC) and virulence factors (ViF) of A. baumannii strain AYE onto strain ATCC19606 to identify them in the latter. We move on to build small networks of VaC and ViF to conceptualize their position in the network space of the whole genomic protein interactome (GPIN) and rationalize their candidature for drugs and/or molecular vaccines. To this end, we propose new sets of known proteins unearthed from interactome built using key factors, KeF, potent enough to compete with VaC and ViF. Our method is the first of its kind to propose, albeit theoretically, a rational approach to identify crucial proteins and pose them for candidates of vaccines and/or drugs effective enough to combat the deadly pathogenic threats of A. baumannii.

Matched MeSH terms: Virulence Factors/genetics
Fulltext Molecular characterization of extended-spectrum β-lactamase-producing Klebsiella pneumoniae from a Malaysian hospital

Mobasseri G, Thong KL, Rajasekaram G, Teh CSJ

Braz J Microbiol, 2020 Mar;51(1):189-195.
PMID: 31838661 DOI: 10.1007/s42770-019-00208-w

Multidrug-resistant (MDR) and extended-spectrum β-lactamase (ESBL)-producing Klebsiella pneumoniae associated with nosocomial infections have caused serious problems in antibiotic management with limited therapeutic choices. This study aimed to determine the genotypic and phenotypic characteristics of K. pneumoniae strains isolated from a tertiary hospital in Malaysia. Ninety-seven clinical K. pneumoniae strains were analyzed for antimicrobial susceptibility, all of which were sensitive to amikacin and colistin (except one strain), while 31.9 % and 27.8 % were MDR and ESBL producers, respectively. PCR and DNA sequencing of the amplicons indicated that the majority of MDR strains (26/27) were positive for blaTEM, followed by blaSHV (24/27), blaCTX-M-1 group (23/27), blaCTX-M-9 group (2/27), and mcr-1 (1/27). Thirty-seven strains were hypervirulent and PCR detection of virulence genes showed 38.1 %, 22.7 %, and 16.5 % of the strains were positive for K1, wabG, and uge genes, respectively. Genotyping by pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST) showed that these strains were genetically diverse and heterogeneous. Sequence types, ST23, ST22, and ST412 were the predominant genotypes. This is the first report of colistin-resistant K. pneumoniae among clinical strains associated with mcr-1 plasmid in Malaysia. The findings in this study have contributed to the effort in combating the increase in antimicrobial resistance by providing better understanding of genotypic characteristics and resistance mechanisms of the organisms.

Matched MeSH terms: Virulence/genetics*
Antimicrobial resistance profiling and molecular typing of methicillin-resistant Staphylococcus aureus isolated from a Malaysian teaching hospital

Noordin A, Sapri HF, Mohamad Sani NA, Leong SK, Tan XE, Tan TL, et al.

J Med Microbiol, 2016 Dec;65(12):1476-1481.
PMID: 27902380 DOI: 10.1099/jmm.0.000387

The annual prevalence of methicillin-resistant Staphylococcus aureus (MRSA) in Malaysia has been estimated to be 30 % to 40 % of all S. aureus infections. Nevertheless, data on the antimicrobial resistance and genetic diversity of Malaysian MRSAs remain few. In 2009, we collected 318 MRSA strains from various wards of our teaching hospital located in Kuala Lumpur, the capital city of Malaysia, and performed antimicrobial susceptibility testing on these strains. The strains were then molecularly characterized via staphylococcal cassette chromosome (SCC) mec and virulence gene (cna, sea, seb, sec, sed, see, seg, seh, sei, eta, etb, Panton-Valentine leukocidin and toxic shock syndrome toxin-1) typing; a subset of 49 strains isolated from the intensive care unit was also typed using PFGE. Most strains were found to be resistant to ciprofloxacin (92.5 %), erythromycin (93.4 %) and gentamicin (86.8 %). The majority (72.0 %) of strains were found to harbour SCCmec type III-SCCmercury with the presence of ccrC, and carried the sea+cna gene combination (49.3 %), with cna as the most prevalent virulence gene (94.0 %) detected. We identified four PFGE clusters, with pulsotype C (n=19) as the dominant example in the intensive care unit, where this pulsotype was found to be associated with carriage of SCCmec type III and the sea gene (P=0.05 and P=0.02, respectively). In summary, the dominant MRSA circulating in our hospital in 2009 was a clone that was ciprofloxacin, erythromycin and gentamicin resistant, carried SCCmec type III-SCCmercury with ccrC and also harboured the sea+cna virulence genes. This clone also appears to be the dominant MRSA circulating in major hospitals in Kuala Lumpur.

Matched MeSH terms: Virulence Factors/genetics
Fulltext Discovery of potential anti-infectives against Staphylococcus aureus using a Caenorhabditis elegans infection model

Kong C, Yehye WA, Abd Rahman N, Tan MW, Nathan S

BMC Complement Altern Med, 2014;14:4.
PMID: 24393217 DOI: 10.1186/1472-6882-14-4

The limited antibiotic options for effective control of methicillin-resistant Staphylococcus aureus infections has led to calls for new therapeutic approaches to combat this human pathogen. An alternative approach to control MRSA is through the use of anti-infective agents that selectively disrupt virulence-mediated pathways without affecting microbial cell viability or by modulating the host natural immune defenses to combat the pathogen.

Matched MeSH terms: Virulence/drug effects
Fulltext Escherichia coli K1 utilizes host macropinocytic pathways for invasion of brain microvascular endothelial cells

Loh LN, McCarthy EMC, Narang P, Khan NA, Ward TH

Traffic, 2017 11;18(11):733-746.
PMID: 28799243 DOI: 10.1111/tra.12508

Eukaryotic cells utilize multiple endocytic pathways for specific uptake of ligands or molecules, and these pathways are commonly hijacked by pathogens to enable host cell invasion. Escherichia coli K1, a pathogenic bacterium that causes neonatal meningitis, invades the endothelium of the blood-brain barrier, but the entry route remains unclear. Here, we demonstrate that the bacteria trigger an actin-mediated uptake route, stimulating fluid phase uptake, membrane ruffling and macropinocytosis. The route of uptake requires intact lipid rafts as shown by cholesterol depletion. Using a variety of perturbants we demonstrate that small Rho GTPases and their downstream effectors have a significant effect on bacterial invasion. Furthermore, clathrin-mediated endocytosis appears to play an indirect role in E. coli K1 uptake. The data suggest that the bacteria effect a complex interplay between the Rho GTPases to increase their chances of uptake by macropinocytosis into human brain microvascular endothelial cells.

Matched MeSH terms: Virulence
Fulltext Multilocus sequence types of clinical Burkholderia pseudomallei isolates from peninsular Malaysia and their associations with disease outcomes

Zueter AR, Rahman ZA, Abumarzouq M, Harun A

BMC Infect Dis, 2018 01 02;18(1):5.
PMID: 29291714 DOI: 10.1186/s12879-017-2912-9

BACKGROUND: Previous studies on the Burkholderia pseudomallei genetic diversity among clinical isolates from melioidosis-endemic areas have identified genetic factors contributing to differential virulence. Although it has been ruled out in Australian and Thai B. pseudomallei populations, it remains unclear whether B. pseudomallei sequence types (STs) correlate with disease in Malaysian patients with melioidosis.
METHODS: In this study, multi-locus sequence typing (MLST) was performed on clinical B. pseudomallei isolates collected from Kelantan state of Malaysia, patients' clinical data were reviewed and then genotype-risk correlations were investigated.
RESULTS: Genotyping of 83 B. pseudomallei isolates revealed 32 different STs, of which 13(40%) were novel. The frequencies of the STs among the 83 isolates ranged from 1 to 12 observations, and ST54, ST371 and ST289 were predominant. All non-novel STs reported in this study have also been identified in other Asian countries. Based on the MLST data analysis, the phylogenetic tree showed clustering of the STs with each other, as well as with the STs from Southeast Asia and China. No evidence for associations between any of B. pseudomallei STs and clinical melioidosis presentation was detected. In addition, the bacterial genotype clusters in relation with each clinical outcome were statistically insignificant, and no risk estimate was reported. This study has expanded the data for B. pseudomallei on MLST database map and provided insights into the molecular epidemiology of melioidosis in Peninsular Malaysia.
CONCLUSION: This study concurs with previous reports concluding that infecting strain type plays no role in determining disease presentation.

Matched MeSH terms: Virulence
Fulltext Changes in the EV-A71 Genome through Recombination and Spontaneous Mutations: Impact on Virulence

Mandary MB, Poh CL

Viruses, 2018 06 12;10(6).
PMID: 29895721 DOI: 10.3390/v10060320

Enterovirus 71 (EV-A71) is a major etiological agent of hand, foot and mouth disease (HFMD) that mainly affects young children less than five years old. The onset of severe HFMD is due to neurological complications bringing about acute flaccid paralysis and pulmonary oedema. In this review, we address how genetic events such as recombination and spontaneous mutations could change the genomic organization of EV-A71, leading to an impact on viral virulence. An understanding of the recombination mechanism of the poliovirus and non-polio enteroviruses will provide further evidence of the emergence of novel strains responsible for fatal HFMD outbreaks. We aim to see if the virulence of EV-A71 is contributed solely by the presence of fatal strains or is due to the co-operation of quasispecies within a viral population. The phenomenon of quasispecies within the poliovirus is discussed to reflect viral fitness, virulence and its implications for EV-A71. Ultimately, this review gives an insight into the evolution patterns of EV-A71 by looking into its recombination history and how spontaneous mutations would affect its virulence.

Matched MeSH terms: Virulence
Fulltext Global and regional dissemination and evolution of Burkholderia pseudomallei

Chewapreecha C, Holden MT, Vehkala M, Välimäki N, Yang Z, Harris SR, et al.

Nat Microbiol, 2017 Jan 23;2:16263.
PMID: 28112723 DOI: 10.1038/nmicrobiol.2016.263

The environmental bacterium Burkholderia pseudomallei causes an estimated 165,000 cases of human melioidosis per year worldwide and is also classified as a biothreat agent. We used whole genome sequences of 469 B. pseudomallei isolates from 30 countries collected over 79 years to explore its geographic transmission. Our data point to Australia as an early reservoir, with transmission to Southeast Asia followed by onward transmission to South Asia and East Asia. Repeated reintroductions were observed within the Malay Peninsula and between countries bordered by the Mekong River. Our data support an African origin of the Central and South American isolates with introduction of B. pseudomallei into the Americas between 1650 and 1850, providing a temporal link with the slave trade. We also identified geographically distinct genes/variants in Australasian or Southeast Asian isolates alone, with virulence-associated genes being among those over-represented. This provides a potential explanation for clinical manifestations of melioidosis that are geographically restricted.

Matched MeSH terms: Virulence
Fulltext Glyoxylate cycle gene ICL1 is essential for the metabolic flexibility and virulence of Candida glabrata

Chew SY, Ho KL, Cheah YK, Ng TS, Sandai D, Brown AJP, et al.

Sci Rep, 2019 02 26;9(1):2843.
PMID: 30808979 DOI: 10.1038/s41598-019-39117-1

The human fungal pathogen Candida glabrata appears to utilise unique stealth, evasion and persistence strategies in subverting the onslaught of host immune response during systemic infection. However, macrophages actively deprive the intracellular fungal pathogen of glucose, and therefore alternative carbon sources probably support the growth and survival of engulfed C. glabrata. The present study aimed to investigate the role of the glyoxylate cycle gene ICL1 in alternative carbon utilisation and its importance for the virulence of C. glabrata. The data showed that disruption of ICL1 rendered C. glabrata unable to utilise acetate, ethanol or oleic acid. In addition, C. glabrata icl1∆ cells displayed significantly reduced biofilm growth in the presence of several alternative carbon sources. It was also found that ICL1 is crucial for the survival of C. glabrata in response to macrophage engulfment. Disruption of ICL1 also conferred a severe attenuation in the virulence of C. glabrata in the mouse model of invasive candidiasis. In conclusion, a functional glyoxylate cycle is essential for C. glabrata to utilise certain alternative carbon sources in vitro and to display full virulence in vivo. This reinforces the view that antifungal drugs that target fungal Icl1 have potential for future therapeutic intervention.

Matched MeSH terms: Virulence
Study on Streptococcus agalactiae infection in Javanese medaka (Oryzias javanicus Bleeker, 1854) model

Amal MNA, Ismail A, Saad MZ, Md Yasin IS, Nasruddin NS, Mastor SS, et al.

Microb Pathog, 2019 Jun;131:47-52.
PMID: 30940607 DOI: 10.1016/j.micpath.2019.03.034

This study determines the median lethal dose, and describes the clinico-pathological changes and disease development following Streptococcus agalactiae infection in Javanese medaka model. Javanese medakas were infected with S. agalactiae via intraperitoneal (IP) from 104 to 108 CFU/mL, and immersion (IM) route from 103 to 107 CFU/mL. The LD50-240h and clinico-pathological changes of the fish was determined until 240 h post infection (hpi). Next, the disease development was determined for 96 hpi in the fish following IP and IM infection at 103 CFU/mL and 104 CFU/mL, respectively. The LD50-240h of S. agalactiae in Javanese medaka was lower following IP injection (4.5 × 102 CFU/mL), compared to IM route (3.5 × 103 CFU/mL). The clinical signs included separating from the schooling group, swimming at the surface of water column, lethargy, erratic swimming pattern, corneal opacity and exophthalmia. Histopathological examinations revealed generalized congestion in almost all internal organs, particularly in liver and brain, while the kidney displayed tubular necrosis. Both IP and IM routes showed significant positive correlation (p 

Matched MeSH terms: Virulence
Role of coaggregation in the pathogenicity and prolonged colonisation of Vibrio cholerae

Toh YS, Yeoh SL, Yap IKS, Teh CSJ, Win TT, Thong KL, et al.

Med Microbiol Immunol, 2019 Dec;208(6):793-809.
PMID: 31263955 DOI: 10.1007/s00430-019-00628-3

Cholera is an acute diarrheal illness caused by the Gram-negative bacterium Vibrio cholerae. The pathogen is known for its ability to form biofilm that confers protection against harsh environmental condition and as part of the colonisation process during infection. Coaggregation is a process that facilitates the formation of biofilm. In a preliminary in vitro study, high coaggregation index and biofilm production were found between V. cholerae with human commensals namely Escherichia coli and Enterobacter cloacae. Building upon these results, the effects of coaggregation were further evaluated using adult BALB/c mouse model. The animal study showed no significant differences in mortality and fluid accumulation ratio between treatment groups infected with V. cholerae alone and those infected with coaggregation partnership (V. cholerae with E. coli or V. cholerae with E. cloacae). However, mild inflammation was detected in both partnering pairs. Higher density of V. cholerae was recovered from faecal samples of mice co-infected with E. coli and V. cholerae in comparison with other groups at 24 h post-infection. This partnership also elicited slightly higher levels of interleukin-5 (IL-5) and interleukin-10 (IL-10). Nonetheless, the involvement of autoinducer-2 (AI-2) as the signalling molecules in quorum sensing system is not evident in this study. Since E. coli is one of the common commensals, our result may suggest the involvement of commensals in cholera development.

Matched MeSH terms: Virulence
Quantitative Proteomics Analysis Revealed Compromised Chicken Dendritic Cells Function at Early Stage of Very Virulent Infectious Bursal Disease Virus Infection

Yasmin AR, Omar AR, Farhanah MI, Hiscox AJ, Yeap SK

Avian Dis, 2019 06 01;63(2):275-288.
PMID: 31251527 DOI: 10.1637/11936-072418-Reg.1

Chicken dendritic cells (DCs) have been demonstrated to be susceptible to infectious bursal disease virus (IBDV), a causative agent of acute and immunosuppressed disease in young chicks known as infectious bursal disease. Further functional characterization of IBDV-infected DCs of chickens is required to provide a better understanding on the influence of the virus on chicken bone marrow-derived dendritic cells (BM-DCs) following very virulent (vv) IBDV infection. Membrane proteins of BM-DCs were extracted and the proteins were further denatured and reduced before performing labeling with isobaric tags for relative and absolute quantitation. The differential expression protein profiles were identified and quantified using liquid chromatography coupled with tandem mass spectrometry, and later validated using flow cytometry and real-time reverse transcriptase PCR. The analysis has identified 134 differentially regulated proteins from a total of 283 proteins (cutoff values of ≤0.67, ≥1.5, and ProtScore >1.3 at 95% confidence interval), which produced high-yield membrane fractions. The entry of vvIBDV into the plasma membrane of BM-DCs was observed at 3 hr postinfection by the disruption of several important protein molecule functions, namely apoptosis, RNA/DNA/protein synthesis, and transport and cellular organization, without the activation of proteins associated with signaling. At the later stage of infection, vvIBDV induced expression of several proteins, namely CD200 receptor 1-A, integrin alpha-5, HSP-90, cathepsin, lysosomal-associated membrane protein, and Ras-related proteins, which play crucial roles in signaling, apoptosis, stress response, and antigen processing as well as in secretion of danger-associated proteins. These findings collectively indicated that the chicken DCs are expressing various receptors regarded as potential targets for pathogen interaction during viral infection. Therefore, fundamental study of the interaction of DCs and IBDV will provide valuable information in understanding the role of professional antigen-presenting cells in chickens and their molecular interactions during IBDV infection and vaccination.

Matched MeSH terms: Virulence
The assimilation of different carbon sources in Candida albicans: Fitness and pathogenicity

Lok B, Adam MAA, Kamal LZM, Chukwudi NA, Sandai R, Sandai D

Med Mycol, 2021 Feb 04;59(2):115-125.
PMID: 32944760 DOI: 10.1093/mmy/myaa080

Candida albicans is a commensal yeast commonly found on the skin and in the body. However, in immunocompromised individuals, the fungi could cause local and systemic infections. The carbon source available plays an important role in the establishment of C. albicans infections. The fungi's ability to assimilate a variety of carbon sources plays a vital role in its colonization, and by extension, its fitness and pathogenicity, as it often inhabits niches that are glucose-limited but rich in alternative carbon sources. A difference in carbon sources affect the growth and mating of C. albicans, which contributes to its pathogenicity as proliferation helps the fungi colonize its environment. The carbon source also affects its metabolism and signaling pathways, which are integral parts of the fungi's fitness and pathogenicity. As a big percentage of the carbon assimilated by C. albicans goes to cell wall biogenesis, the availability of different carbon sources will result in cell walls with variations in rigidity, adhesion, and surface hydrophobicity. In addition to the biofilm formation of the fungi, the carbon source also influences whether the fungi grow in yeast- or mycelial-form. Both forms play different roles in C. albicans's infection process. A better understanding of the role of the carbon sources in C. albicans's pathogenicity would contribute to more effective treatment solutions for fungal infections.

Matched MeSH terms: Virulence
Fulltext Molecular and pathogenicity of infectious bronchitis virus (Gammacoronavirus) in Japanese quail (Coturnix japonica)

Fadhilah AS, Kai TH, Lokman HI, Yasmin NAR, Hafandi A, Hasliza AH, et al.

Poult Sci, 2020 Jun;99(6):2937-2943.
PMID: 32475428 DOI: 10.1016/j.psj.2020.01.026

Infectious bronchitis virus (IBV) infection is highly infectious respiratory disease in poultry industry with significant economic importance. The prevalence of IBV in quail industry in Malaysia was not well documented; therefore, its actual role in the epidemiology of the disease is relatively unknown. This study was to determine the susceptibility of Japanese quail, as one of the species in commercial poultry industry, toward IBV. In addition, it will also give a potential impact on the overall health management in the quail industry even though it had been established that quail are resistant to diseases affecting poultry. Moreover, to the best of our knowledge, it is the first experimental study on IBV inoculation in quail. In this experimental study, 20 quails were divided into 4 groups (n = 5 for group A, B, and C, n = 5 for control group). The quails in group A, B, and C were infected via intraocular and intranasal routes with 0.2 mL of 10 × 5 EID50 of the virus. Clinical signs, gross lesions, positive detection of virus, and trachea histopathological scoring were used to assess the susceptibility of these Japanese quails. The results have indicated mild ruffled feathers and watery feces in these inoculated birds. Trachea, lung, and kidney were subjected to one-step reverse transcription polymerase chain reaction for virus detection. The virus was found from trachea and lung samples, whereas it was absent from all kidney samples. Only 3 quails were found with gross lesions. There was a significant difference of tracheal lesion by 0.009 ± 0.845 (P < 0.05) within the treatment groups. In summary, Japanese quails might be susceptible to IBV.

Matched MeSH terms: Virulence
In vitro study of Pasteurella multocida adhesion to trachea, lung and aorta of rabbits

Al-Haddawi MH, Jasni S, Zamri-Saad M, Mutalib AR, Zulkifli I, Son R, et al.

Vet J, 2000 May;159(3):274-81.
PMID: 10775473

In vitro experiments were undertaken to study the adhesion and colonization to tracheal mucosa, lung and aorta explants from freshly killed rabbits of two different strains of Pasteurella multocida. Serotype A:3 (capsulated, fimbriae +, haemagglutination -, dermonecrotic toxin -) isolated from a rabbit with rhinitis, and serotype D:1 (non-capsulated, fimbriae +, haemagglutination +, dermonecrotic toxin +) isolated from a dead rabbit with septicaemia, were used. When the explants were observed under the scanning electron microscope, the type D strain was highly adherent to trachea and aorta explants compared to the type A strain. Adhesion to lung explants was best achieved by the type A strain after 45 min incubation, but after 2 h incubation no significant difference was observed between the strains. Our data indicate that the presence of fimbriae and the absence of capsule seem to enhance the adherence of P. multocida type D strain to tracheal tissue. The capsular material of P. multocida type A strain and the toxin of the type D strain seem to influence the adherence to lung tissue in rabbit. Adhesion of strain D to aorta may indicate the expression of receptors on the endothelium to that strain and may also explain the ability of certain strains to cause septicaemia.

Matched MeSH terms: Virulence

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