Browsing by Subject "Skin infection"

Now showing 1 - 4 of 4
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    Dispensability of Ascorbic Acid Uptake and Utilization Encoded by ulaABCD for the Virulence of Haemophilus ducreyi in Humans
    (Oxford University Press, 2023) Brothwell, Julie A.; Fortney, Kate R.; Batteiger, Teresa; Katz, Barry P.; Spinola, Stanley M.; Microbiology and Immunology, School of Medicine
    Compared with wounded skin, ascorbic acid is enriched in pustules of humans experimentally infected with Haemophilus ducreyi. Compared with the broth-grown inocula, transcription of the H. ducreyi ulaABCD operon, which encodes genes for ascorbic acid uptake, is increased in pustules. We hypothesized that ascorbic acid uptake plays a role in H. ducreyi virulence. Five volunteers were infected with both H. ducreyi strain 35000HP and its isogenic ulaABCD deletion mutant at multiple sites; the papule and pustule formation rates of the mutant and parent strains were similar. Thus, ascorbic acid uptake is not essential for H. ducreyi virulence in humans.
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    Formate production is dispensable for Haemophilus ducreyi virulence in human volunteers
    (American Society for Microbiology, 2023) Brothwell, Julie A.; Fortney, Kate R.; Williams, Jalan S.; Batteiger, Teresa A.; Duplantier, Rory; Grounds, Danielle; Jannasch, Amber S.; Katz, Barry P.; Spinola, Stanley M.; Microbiology and Immunology, School of Medicine
    Haemophilus ducreyi is a causative agent of cutaneous ulcers in children who live in the tropics and of the genital ulcer disease chancroid in sexually active persons. In the anaerobic environment of abscesses and ulcers, anaerobic respiration and mixed acid fermentation (MAF) can be used to provide cellular energy. In Escherichia coli, MAF produces formate, acetate, lactate, succinate, and ethanol; however, MAF has not been studied in H. ducreyi. In human challenge experiments with H. ducreyi 35000HP, transcripts of the formate transporter FocA and pyruvate formate lyase (PflB) were upregulated in pustules compared to the inocula. We made single and double mutants of focA and pflB in 35000HP. Growth of 35000HPΔfocA was similar to 35000HP, but 35000HPΔpflB and 35000HPΔfocA-pflB had growth defects during both aerobic and anaerobic growth. Mutants lacking pflB did not secrete formate into the media. However, formate was secreted into the media by 35000HPΔfocA, indicating that H. ducreyi has alternative formate transporters. The pH of the media during anaerobic growth decreased for 35000HP and 35000HPΔfocA, but not for 35000HPΔpflB or 35000HPΔfocA-pflB, indicating that pflB is the main contributor to media acidification during anaerobic growth. We tested whether formate production and transport were required for virulence in seven human volunteers in a mutant versus parent trial between 35000HPΔfocA-pflB and 35000HP. The pustule formation rate was similar for 35000HP (42.9%)- and 35000HPΔfocA-pflB (62%)-inoculated sites. Although formate production occurs during in vitro growth and focA-pflB transcripts are upregulated during human infection, focA and pflB are not required for virulence in humans.
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    Leukotriene B4 levels determine staphylococcus aureus skin infection outcome
    (2017-08-18) Brandt, Stephanie Lillian; Serezani, Henrique; Blum, Janice; Kaplan, Mark H.; Evans-Molina, Carmella
    Methicillin-resistant Staphylococcus aureus (MRSA) is a major cause of severe skin infections and due to antibiotic resistance there is an intrinsic need to develop new immunotherapeutic strategies. Skin immune responses to infections require the cross-talk between phagocytes and structural cells that involves the secretion of cytokines, chemokines, and lipids. Leukotriene B4 (LTB4) is a pleiotropic lipid mediator known as a chemoattractant, but is also necessary to promote antimicrobial activity through B leukotriene receptor 1 (BLT1) signaling. However, chronic LTB4 production is associated with inflammatory diseases, including diabetes. People with diabetes are more susceptible to infections. The determinants by which LTB4/BLT1 promotes protective or detrimental immune responses in homeostasis and diabetes are unknown. We hypothesize that LTB4 levels determine infection outcome; while LTB4 is necessary for infection control, excessive LTB4 levels promote overwhelming inflammation that impairs host defense. Our data show that skin macrophages were necessary for LTB4 production and that LTB4 was vital for neutrophil direction, abscess formation, IL 1β production, and MRSA clearance through reactive oxygen species production. Importantly, topical LTB4 ointment treatment enhances neutrophil direction, abscess formation, and bacterial clearance. Conversely, in the setting of diabetes, skin macrophages drove excessive LTB4 production that promoted overwhelming inflammation, uncontrolled neutrophil recruitment, poor abscess formation, and lack of bacterial control. Diabetic mice treated with a topical ointment to inhibit BLT1 dampened inflammation and restored host defense by improving abscess formation, bacterial clearance, and overall inflammatory responses in the skin. These data demonstrate the balance of LTB4-induced inflammation is critical for regulating optimal immune responses during infections. This work highlights the importance of investigating the role of inflammatory mediators in the settings of health and disease. Targeting LTB4/BLT1 has therapeutic potential to regulate inflammation during MRSA skin infection by enhancing immune responses in settings of vulnerability or decrease inflammation in diabetes.
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    Prevalence, Clinical Features, and Antibiotic Susceptibility of Group A Streptococcal Skin Infections in Schoolchildren in Urban Western and Northern Uganda
    (Wolters Kluwer, 2019) Chang, Aileen Y.; Scheel, Amy; Dewyer, Alyssa; Hovis, Ian W.; Sarnacki, Rachel; Aliku, Twalib; Okello, Emmy; Bwanga, Freddie; Sable, Craig; Maurer, Toby A.; Beaton, Andrea Z.; Dermatology, School of Medicine
    Background: Group A Streptococcus (GAS) skin infections can lead to invasive sepsis, poststreptococcal glomerulonephritis, and potentially rheumatic heart disease (RHD). Within a study to identify predisposing factors of RHD in Ugandan schoolchildren, we determined the prevalence of skin infections and assessed the clinical features and antibiotic susceptibility of GAS skin infection. Methods: Cross-sectional study conducted at 3 urban primary schools in Western and Northern Uganda in March 2017. A dermatologist rendered clinical diagnoses and obtained a skin swab specimen from lesions with signs of bacterial infection. Beta-hemolytic colonies underwent Lancefield grouping, species identification by polymerase chain reaction and antimicrobial susceptibility testing. Results: From 3265 schoolchildren, we observed 32% with ≥1 fungal, 1.8% with ≥1 bacterial, 0.9% with ≥1 viral, and 0.2% with ≥1 ectoparasitic infection. Of 79, 25 (32%) specimens were GAS-positive, of which one-third demonstrated tetracycline resistance. Of 17 impetigo cases, 13 (76%) were located on the leg/foot and 3 (18%) on the head/neck. Prevalence of GAS skin infection was 0.8% (25 of 3265). In Northern Uganda, where subclinical definite RHD prevalence is 1.1%, GAS skin infection prevalence was 1.2% (4 of 343) and 0.9% (3 of 352). Conclusion: This study identifies tetracycline-resistant GAS in Ugandan communities, suggests modified skin examination of exposed anatomic locations may be appropriate for population-based GAS skin infection studies, and underscores need for clear case definitions of GAS skin infection. Future studies are needed to evaluate the role of GAS skin infection in development of RHD in Ugandan communities.