Biotyping and Virulence Properties of Skin Isolates ofCandida parapsilosis

The biotype and virulence of skin isolates of Candida parapsilosis were compared with blood isolates of the same fungus. Morphotype, resistotype, and electrophoretic karyotype determinations did not reveal any special cluster with a unique or dominant pathogenic feature among all of the isolates, regardless of their source. However, all cutaneous isolates had uniformly elevated secretory aspartyl-protease (Sap) activity, more than four times higher than the enzyme activity of the blood isolates. They were also highly vaginopathic in a rat vaginitis model, being significantly more virulent than blood isolates in this infection model. In contrast, skin isolates were nonpathogenic in systemic infection of cyclophosphamide-immunodepressed mice, while some blood isolates were, in this model, highly pathogenic (median survival time, 2 days, with internal organ invasion at autopsy). Finally, skin isolates did not differ, as a whole, from blood isolates in their adherence to plastic. This property was associated with a morphotype, as defined by a colony with continuous fringe, which was present among both skin and blood isolates. While confirming the genetic heterogenicity of C. parapsilosis, our data strongly suggest that the potential of this fungus to cause mucosal disease is associated with Sap production and is substantially distinct from that of systemic invasion.

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Identification and Characterization of TUP1-Regulated Genes in Candida albicans

Genetics ◽

10.1093/genetics/156.1.31 ◽

2000 ◽

Vol 156 (1) ◽

pp. 31-44 ◽

Cited By ~ 7

Author(s):

Burkhard R Braun ◽

W Steven Head ◽

Ming X Wang ◽

Alexander D Johnson

Keyword(s):

Candida Albicans ◽

Systemic Infection ◽

Subtractive Hybridization ◽

Filamentous Growth ◽

Surface Proteins ◽

Infection Model ◽

Ferric Reductase ◽

Pathogenesis Related Protein ◽

Plant Pathogenesis ◽

Rnase T2

Abstract TUP1 encodes a transcriptional repressor that negatively controls filamentous growth in Candida albicans. Using subtractive hybridization, we identified six genes, termed repressed by TUP1 (RBT), whose expression is regulated by TUP1. One of the genes (HWP1) has previously been characterized, and a seventh TUP1-repressed gene (WAP1) was recovered due to its high similarity to RBT5. These genes all encode secreted or cell surface proteins, and four out of the seven (HWP1, RBT1, RBT5, and WAP1) encode putatively GPI-modified cell wall proteins. The remaining three, RBT2, RBT4, and RBT7, encode, respectively, an apparent ferric reductase, a plant pathogenesis-related protein (PR-1), and a putative secreted RNase T2. The expression of RBT1, RBT4, RBT5, HWP1, and WAP1 was induced in wild-type cells during the switch from the yeast form to filamentous growth, indicating the importance of TUP1 in regulating this process and implicating the RBTs in hyphal-specific functions. We produced knockout strains in C. albicans for RBT1, RBT2, RBT4, RBT5, and WAP1 and detected no phenotypes on several laboratory media. However, two animal models for C. albicans infection, a rabbit cornea model and a mouse systemic infection model, revealed that rbt1Δ and rbt4Δ strains had significantly reduced virulence. TUP1 appears, therefore, to regulate many genes in C. albicans, a significant fraction of which are induced during filamentous growth, and some of which participate in pathogenesis.

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Systemic Infection Due to Candida parapsilosis in a Domestic Ferret (Mustela putorius furo)

Journal of Exotic Pet Medicine ◽

10.1053/j.jepm.2013.11.013 ◽

2014 ◽

Vol 23 (1) ◽

pp. 85-90 ◽

Cited By ~ 3

Author(s):

Elisabetta Mancinelli ◽

Anna L. Meredith ◽

Mark F. Stidworthy

Keyword(s):

Candida Parapsilosis ◽

Systemic Infection ◽

Mustela Putorius ◽

Mustela Putorius Furo

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Dual Transcriptomic Analyses Unveil Host–Pathogen Interactions Between Salmonella enterica Serovar Enteritidis and Laying Ducks (Anas platyrhynchos)

Frontiers in Microbiology ◽

10.3389/fmicb.2021.705712 ◽

2021 ◽

Vol 12 ◽

Author(s):

Yu Zhang ◽

Lina Song ◽

Lie Hou ◽

Zhengfeng Cao ◽

Wanwipa Vongsangnak ◽

...

Keyword(s):

Food Poisoning ◽

Systemic Infection ◽

Egg Laying ◽

Cytokine Receptor ◽

Differentially Expressed ◽

Receptor Interaction ◽

Infection Model ◽

Host Pathogen Interactions ◽

Related Factors ◽

Host Pathogen

Salmonella enteritidis (SE) is a pathogen that can readily infect ovarian tissues and colonize the granulosa cell layer such that it can be transmitted via eggs from infected poultry to humans in whom it can cause food poisoning. Ducks are an important egg-laying species that are susceptible to SE infection, yet the host–pathogen interactions between SE and ducks have not been thoroughly studied to date. Herein, we performed dual RNA-sequencing analyses of these two organisms in a time-resolved infection model of duck granulosa cells (dGCs) by SE. In total, 10,510 genes were significantly differentially expressed in host dGCs, and 265 genes were differentially expressed in SE over the course of infection. These differentially expressed genes (DEGs) of dGCs were enriched in the cytokine–cytokine receptor interaction pathway via KEGG analyses, and the DEGs in SE were enriched in the two-component system, bacterial secretion system, and metabolism of pathogen factors pathways as determined. A subsequent weighted gene co-expression network analysis revealed that the cytokine–cytokine receptor interaction pathway is mostly enriched at 6 h post-infection (hpi). Moreover, a number of pathogenic factors identified in the pathogen–host interaction database (PHI-base) are upregulated in SE, including genes encoding the pathogenicity island/component, type III secretion, and regulators of systemic infection. Furthermore, an intracellular network associated with the regulation of SE infection in ducks was constructed, and 16 cytokine response-related dGCs DEGs (including IL15, CD40, and CCR7) and 17 pathogenesis-related factors (including sseL, ompR, and fliC) were identified, respectively. Overall, these results not only offer new insights into the mechanisms underlying host–pathogen interactions between SE and ducks, but they may also aid in the selection of potential targets for antimicrobial drug development.

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1366. In Vitro and In Vivo Activity of Cefiderocol against Stenotrophomonas maltophilia Clinical Isolates

Open Forum Infectious Diseases ◽

10.1093/ofid/ofy210.1197 ◽

2018 ◽

Vol 5 (suppl_1) ◽

pp. S418-S418 ◽

Cited By ~ 2

Author(s):

Akinobu Ito ◽

Merime Ota ◽

Rio Nakamura ◽

Masakatsu Tsuji ◽

Takafumi Sato ◽

...

Keyword(s):

Stenotrophomonas Maltophilia ◽

Systemic Infection ◽

Vitro Activity ◽

Clinical Isolates ◽

Infection Model ◽

In Vitro Activity ◽

In Vivo Efficacy ◽

Broth Microdilution Method

Abstract Background Cefiderocol (S-649266, CFDC) is a novel siderophore cephalosporin against Gram-negatives, including carbapenem (CR)-resistant strains. Its spectrum includes both the Enterobacteriaceae but also nonfermenters, including Stenotrophomonas maltophilia—an opportunistic pathogen with intrinsic resistance to carbapenem antibiotics. In this study, in vitro activity and in vivo efficacy of CFDC and comparators against S. maltophilia were determined. Methods MICs of CFDC and comparators (trimethoprim/sulfamethoxazole (TMP/SMX), minocycline (MINO), tigecycline (TGC), ciprofloxacin (CPFX), cefepime (CFPM), meropenem (MEPM), and colistin (CL)) were determined by broth microdilution method as recommended by CLSI. The MIC against CFDC was determined using iron-depleted cation-adjusted Mueller–Hinton broth. In vivo efficacy of CFDC, CFPM, ceftazidime–avibactam (CAZ/AVI), MEPM, and CL was evaluated using neutropenic murine systemic infection model caused by strain SR21970. The 50% effective doses (ED50s) were calculated by the logit method using the survival number at each dose 7 days after infection. Results MIC90 of CFDC and comparators against the 216 clinical isolates from global countries collected in SIDERO-CR 2014/2016 study are shown in the table. CFDC, TMP/SMX, MINO, and TGC showed good activity with MIC90 of 0.5, 0.25/4.75, 1, and 2 µg/mL, respectively. CFDC, MINO, and TGC inhibited growth of all tested strains at ≤1, ≤4, and ≤8 µg/mL although two strains showed resistance to TMP/SMX. MICs of CFPM, CAZ/AVI, MEPM, and CL were ≥32 µg/mL. The ED50 of CFDC against S. maltophilia SR21970 with MIC of 0.125 mg/mL was 1.17 mg/kg/dose. Conversely, MICs of CFPM, CAZ/AVI, MEPM/CS, and CL against SR21970 were 32 μg/mL or higher, and ED50s were >100 mg/kg/dose, showing that CFDC had potent in vivo efficacy against S. maltophilia strain which was resistant to other antibiotics. Conclusion CFDC showed potent in vitro activity against S. maltophilia, including TMP/SMX-resistant isolates. CFDC also showed potent in vivo efficacy reflecting in vitro activity against S. maltophilia in murine systemic infection model. Disclosures A. Ito, Shionogi & Co., Ltd.: Employee, Salary. M. Ota, Shionogi & Co., Ltd.: Employee, Salary. R. Nakamura, Shionogi & Co., Ltd.: Employee, Salary. M. Tsuji, Shionogi & Co., Ltd.: Employee, Salary. T. Sato, Shionogi & Co., Ltd.: Employee, Salary. Y. Yamano, Shionogi & Co., Ltd.: Employee, Salary.

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Contribution of the Major Secreted Yops of Yersinia enterocolitica O:8 to Pathogenicity in the Mouse Infection Model

Infection and Immunity ◽

10.1128/iai.72.9.5227-5234.2004 ◽

2004 ◽

Vol 72 (9) ◽

pp. 5227-5234 ◽

Cited By ~ 117

Author(s):

Konrad Trülzsch ◽

Thorsten Sporleder ◽

Emeka I. Igwe ◽

Holger Rüssmann ◽

Jürgen Heesemann

Keyword(s):

Small Intestine ◽

Systemic Infection ◽

Effector Proteins ◽

Infection Model ◽

Virulence Plasmid ◽

The Novel ◽

Serotype O ◽

Mouse Infection Model ◽

Mouse Tissues ◽

First Time

ABSTRACT Pathogenic yersiniae (Yersinia pestis, Y. pseudotuberculosis, and Y. enterocolitica) harbor a 70-kb virulence plasmid (pYV) that encodes a type III secretion system and a set of at least six effector proteins (YopH, YopO, YopP, YopE, YopM, and YopT) that are injected into the host cell cytoplasm. Yops (Yersinia outer proteins) disturb the dynamics of the cytoskeleton, inhibit phagocytosis by macrophages, and downregulate the production of proinflammatory cytokines, which makes it possible for yersiniae to multiply extracellularly in lymphoid tissue. Y. enterocolitica serotype O:8 belongs to the highly mouse-pathogenic group of yersiniae in contrast to Y. enterocolitica serotype O:9. However, there has been no systematic study of the contribution of Yops to the pathogenicity of Y. enterocolitica O:8 in mice. We generated a set of yop gene deletion mutants of Y. enterocolitica O:8 by using the novel Red cloning procedure. We subsequently analyzed the contribution of yopH, -O, -P, -E, -M, -T, and -Q deletions to pathogenicity after oral and intravenous infection of mice. Here we showed for the first time that a ΔyopT deletion mutant colonizes mouse tissues to a greater extent than the parental strain. The ΔyopO, ΔyopP, and ΔyopE mutants were only slightly attenuated after oral infection since they were still able to colonize the spleen and liver and cause systemic infection. The ΔyopO mutant was lethal for mice, whereas ΔyopP and ΔyopE mutants were successfully eliminated from the spleen and liver 2 weeks after infection. In contrast the ΔyopH, ΔyopM, and ΔyopQ mutants were highly attenuated and not able to colonize the spleen and liver on any of the days tested. The ΔyopH, ΔyopO, ΔyopP, ΔyopE, ΔyopM, and ΔyopQ mutants had only modest defects in the colonization of the small intestine and Peyer's patches. The ΔyopE mutant was eliminated from the small intestine 3 weeks after infection, whereas the ΔyopH, ΔyopP, ΔyopM, and ΔyopQ mutants continued to colonize the small intestine at this time.

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Macrophages target Salmonella by Lc3-associated phagocytosis in a systemic infection model

Autophagy ◽

10.1080/15548627.2019.1569297 ◽

2019 ◽

Vol 15 (5) ◽

pp. 796-812 ◽

Cited By ~ 17

Author(s):

Samrah Masud ◽

Tomasz K. Prajsnar ◽

Vincenzo Torraca ◽

Gerda E.M. Lamers ◽

Marianne Benning ◽

...

Keyword(s):

Systemic Infection ◽

Infection Model

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An original infection model identifies host lipoprotein import as a route for blood-brain barrier crossing

Nature Communications ◽

10.1038/s41467-020-19826-2 ◽

2020 ◽

Vol 11 (1) ◽

Author(s):

Billel Benmimoun ◽

Florentia Papastefanaki ◽

Bruno Périchon ◽

Katerina Segklia ◽

Nicolas Roby ◽

...

Keyword(s):

Blood Brain Barrier ◽

Ldl Receptor ◽

Systemic Infection ◽

Brain Barrier ◽

Infection Model ◽

Brain Infection ◽

Blood Brain ◽

Group B

AbstractPathogens able to cross the blood-brain barrier (BBB) induce long-term neurological sequelae and death. Understanding how neurotropic pathogens bypass this strong physiological barrier is a prerequisite to devise therapeutic strategies. Here we propose an innovative model of infection in the developing Drosophila brain, combining whole brain explants with in vivo systemic infection. We find that several mammalian pathogens are able to cross the Drosophila BBB, including Group B Streptococcus (GBS). Amongst GBS surface components, lipoproteins, and in particular the B leucine-rich Blr, are important for BBB crossing and virulence in Drosophila. Further, we identify (V)LDL receptor LpR2, expressed in the BBB, as a host receptor for Blr, allowing GBS translocation through endocytosis. Finally, we show that Blr is required for BBB crossing and pathogenicity in a murine model of infection. Our results demonstrate the potential of Drosophila for studying BBB crossing by pathogens and identify a new mechanism by which pathogens exploit the machinery of host barriers to generate brain infection.

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Pathologic Findings and Viral Antigen Distribution During Natural Infection of Ring-Necked Pheasants With H5N2 Highly Pathogenic Avian Influenza Virus A

Veterinary Pathology ◽

10.1177/0300985816671377 ◽

2016 ◽

Vol 54 (2) ◽

pp. 312-315 ◽

Cited By ~ 2

Author(s):

D. K. Ajithdoss ◽

M. K. Torchetti ◽

L. Badcoe ◽

D. S. Bradway ◽

T. V. Baszler

Keyword(s):

Avian Influenza ◽

Viral Antigen ◽

Highly Pathogenic Avian Influenza ◽

Natural Infection ◽

Systemic Infection ◽

Viral Disease ◽

Acute Onset ◽

Pathologic Finding ◽

Highly Pathogenic ◽

Pathogenic Avian Influenza

Highly pathogenic avian influenza (HPAI) is a major viral disease of poultry characterized by acute onset, systemic infection, and rapid death. In January 2015, H5N2 HPAI was identified by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) and gene sequencing as the cause of rapid death in 40 of 390 ring-necked pheasants (approximately 10% mortality), raised in a game bird farm in Washington State. We report clinicopathologic findings and viral antigen distribution in pheasants that died during the outbreak. Affected birds were depressed with reluctance to move, ruffled feathers, and drooping heads. Congestion of the cerebellar meningeal blood vessels was the only consistent gross pathologic finding. Meningoencephalitis with vasculitis and necrosis in the spleen and heart were the major microscopic lesions in the birds. Viral antigen was consistently detected in the brain, heart, and ovary with variable presence in other organs.

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Galleria mellonellaas an infection model for the multi-host pathogenStreptococcus agalactiaereflects hypervirulence of ST283

10.1101/407171 ◽

2018 ◽

Author(s):

Anne Six ◽

Sakranmanee Kranjangwong ◽

Margaret Crumlish ◽

Ruth Zadoks ◽

Daniel Walker

Keyword(s):

Low Cost ◽

Group B Streptococcus ◽

Systemic Infection ◽

Invasive Disease ◽

Larval Survival ◽

Infection Model ◽

Virulence Determinants ◽

Bacterial Replication ◽

Group B ◽

Dose Dependent

AbstractStreptococcus agalactiae, or group B streptococcus (GBS), infects diverse hosts including humans, economically important livestock and fishes. In the context of human health, GBS is a major cause of neonatal infections and an emerging cause of invasive disease in adults. Here we show that GBS is able to establish a systemic infection inG. mellonellalarvae that is associated with extensive bacterial replication and dose dependent larval survival. This infection model is suitable for use with GBS isolates from both homeothermic and poikilothermic hosts and a hypervirulent sequence type (ST) associated with invasive human disease, ST283, shows increased virulence in this model, indicating it may be useful in studying GBS virulence determinants. In addition, we demonstrate that larval survival can be afforded by antibiotic treatment and so the model may also be useful in the development of novel anti-GBS strategies. The use ofG. mellonellain GBS research has the potential to provide a low cost infection model that could reduce the number of vertebrates used in the study of GBS infection.

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Insight Into the Virulence Related Secretion Systems, Fimbriae, and Toxins in O2:K1 Escherichia coli Isolated From Bovine Mastitis

Frontiers in Veterinary Science ◽

10.3389/fvets.2021.622725 ◽

2021 ◽

Vol 8 ◽

Author(s):

Min Sun ◽

Xing Gao ◽

Kejie Zhao ◽

Jiale Ma ◽

Huochun Yao ◽

...

Keyword(s):

Escherichia Coli ◽

Bovine Mastitis ◽

Systemic Infection ◽

Infection Model ◽

Secretion Systems ◽

E Coli ◽

Bacterial Pathogenicity ◽

Mouse Infection Model ◽

Type Iv ◽

Mouse Infection

Mastitis remains a major infection of dairy cows and an important issue for the dairy farmers, and Escherichia coli (E. coli) bovine mastitis is a disease of significant economic importance in the dairy industry. Our study identified six isolates belong to phylogroup B2 from 69 bovine mastitis E. coli strains. Except for one serotype O1 strain, all group B2 isolates were identified into serotype O2 and showed significantly higher mortality in the mouse infection than other phylogroups' strains. Genomic analyses and further tests were performed to examine the role of secretion systems, fimbriae, and toxins during the systemic infection of O2:K1 strain BCE049. Two integral T6SS loci and three predicted effectors clusters were found to assemble the functional T6SS complex and deliver diverse toxic effectors to modulate bacterial virulence in the mouse infection model. A total of four T4SS loci were harbored in the BCE049 genome, three of them are encoded in different plasmids, respectively, whereas the last one locates within the bacterial chromosome at FQU84_16715 to FQU84_16760, and was significantly involved in the bacterial pathogenicity. Numerous predicted pilus biosynthesis gene loci were found in the BCE049 genome, whereas most of them lost long fragments encoding key genes for the pili assembly. Unexpectedly, a type IV pilus gene locus locating at FQU84_01405 to FQU84_01335 in the plasmid 2, was found to be required for the full virulence of mastitis strain BCE049. It should be noted that a genetic neighborhood inserted with diverse genes is encoded by the plasmid 1, which harbors three prominent toxins including β-hemolysin, cytotoxic necrotizing factor 2 and cytolethal distending toxin type III. Consequent studies verified that these toxins significantly contributed to the bacterial pathogenicity. These findings provide a molecular blueprint for understanding the underlying mechanisms employed by the bovine mastitis E. coli to colonize in host and cause systemic infection.

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