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1.
BMC Infect Dis ; 24(1): 425, 2024 Apr 22.
Article in English | MEDLINE | ID: mdl-38649870

ABSTRACT

BACKGROUND: Necrotising fasciitis (NF) is a life-threatening soft-tissue infection that rapidly destroys the epidermis, subcutaneous tissue, and fascia. Despite their low virulence, Lactobacillus spp. can cause NF, and because of its rare incidence, there is limited information about its molecular and clinicopathological characteristics. We report a rare case of NF in a patient with type 2 diabetes mellitus diagnosed on admission and severe obesity due to infection with two types of Lactobacillus spp. that manifested in extensive necrosis. CASE PRESENTATION: A 48-year-old woman was referred to our hospital with a complaint of difficulty walking due to severe bilateral thigh pain. She presented with mild erythema, swelling, and severe skin pain extending from the pubic region to the groin. The patient was morbidly obese, had renal dysfunction, and had diabetes mellitus diagnosed on admission.; her LRINEC (Laboratory Risk Indicator for Necrotising Fasciitis) score was 9, indicating a high risk of NF. An exploratory surgical incision was made, and NF was diagnosed based on fascial necrosis. Emergent surgical debridement was performed, and cultures of the tissue culture and aspirated fluid/pus revealed two types of Lactobacillus spp.: Lactobacillus salivarius and L. iners. The patient was admitted to the intensive care unit (ICU), where antibiotics were administered and respiratory and circulatory management was performed. Diabetic ketoacidosis was detected, which was treated by controlling the blood glucose level stringently via intravenous insulin infusion. The patient underwent a second debridement on day 11 and a skin suture and skin grafting on day 36. The patient progressed well, was transferred from the ICU to the general ward on day 41, and was discharged unassisted on day 73. CONCLUSIONS: Lactobacillus spp. are rarely pathogenic to healthy individuals and can scarcely trigger NF. However, these bacteria can cause rare infections such as NF in immunocompromised individuals, such as those with diabetes and obesity, and an early diagnosis of NF is imperative; surgical intervention may be required for the prevention of extensive necrosis. The LRINEC score may be useful for the early diagnosis of NF, even for less pathogenic bacteria such as Lactobacillus.


Subject(s)
Fasciitis, Necrotizing , Lactobacillus , Humans , Fasciitis, Necrotizing/microbiology , Fasciitis, Necrotizing/pathology , Female , Middle Aged , Lactobacillus/isolation & purification , Diabetes Mellitus, Type 2/complications , Anti-Bacterial Agents/therapeutic use , Debridement , Necrosis/microbiology , Gram-Positive Bacterial Infections/microbiology , Gram-Positive Bacterial Infections/diagnosis , Gram-Positive Bacterial Infections/drug therapy , Gram-Positive Bacterial Infections/pathology
2.
Int. j. morphol ; 41(2): 423-430, abr. 2023. ilus, tab
Article in English | LILACS | ID: biblio-1440305

ABSTRACT

SUMMARY: Cervical necrotizing fasciitis (NF) is a rare complication of oral cavity infection with high morbi-mortality. Given its low prevalence, adequately reporting cases of NF, its therapeutic management, and associated morphofunctional modifications to the clinical and scientific community is pivotal. To that end, we herein describe a case of cervical NF in a 60-year-old patient with comorbidities and patient presented large, painful cervical swelling associated with a necrotic ulcer lesion in the anterior neck region. Intraoral examination indicated a periodontal abscess in the right mandibular area, while computed tomography indicated the lesion's extension from the right mandibular to the submandibular region. Following empirical intravenous antibiotic treatment, a broad surgical debridement was performed, and the foci of oral infection were removed. Debridement revealed communication between deep and superficial anatomical regions in the submandibular area, where we subsequently placed a Penrose drain. Biopsies showing acute inflammatory infiltrate associated with necrotic and hemorrhagic regions confirmed the diagnosis of NF. When an antibiogram revealed resistance to the empirical treatment, the antibiotic scheme was replaced with an adequate alternative. After a second debridement, we closed the defect with fascio-mucocutaneous advancement flaps with a lateral base while maintaining suction drainage. Having reacted positively, the patient was discharged 10 days after the operation. Despite an extensive morphofunctional change generated in the treated area, the patient showed no difficulties with breathing, phonation, swallowing, or mobilizing the area during control sessions. Altogether, this report contributes to the highly limited literature describing morphological aspects that can facilitate or delay the spread of infection or the morphofunctional disorders associated with the size and depth of surgical interventions for cervical NF, information that is relevant for the comprehensive, long-term prognosis of the treatment of NF.


La fascitis necrosante (FN) cervical es una rara complicación de una infección proveniente de la cavidad bucal asociada a una alta morbimortalidad. Por lo anterior, es fundamental informar a la comunidad clínica y científica los casos de FN, su manejo terapéutico y las modificaciones morfofuncionales asociadas. Se describe un caso de FN cervical en una paciente de 60 años quien presentó una gran tumefacción dolorosa asociada a una lesión ulcerosa necrótica en la región anterior del cuello. El examen intraoral mostró un absceso periodontal en el área mandibular derecha y la tomografía computarizada mostró la extensión de la lesión hacia la región submandibular. Tras el tratamiento antibiótico empírico, se realizó un desbridamiento quirúrgico extenso y se extirparon los focos de infección oral. El desbridamiento reveló comunicación entre las regiones anatómicas profundas y superficiales del área submandibular, donde se colocó un drenaje Penrose. Las biopsias mostraron un infiltrado inflamatorio agudo asociado con regiones necróticas y hemorrágicas, confirmando el diagnóstico de FN. El antibiograma reveló resistencia al tratamiento empírico, por lo que el esquema antibiótico se sustituyó. Tras un segundo desbridamiento, se cerró el defecto con colgajos de avance fascio-mucocutáneos de base lateral manteniendo drenaje aspirativo. El positivo progreso del paciente permitió su alta 10 días después. Aun cuando se generó una gran modificación morfofuncional en el área tratada, la paciente no presentó dificultades para respirar, hablar, deglutir o movilizar el área cervical intervenida durante las sesiones de control. Este informe contribuye a la limitada literatura que describe los aspectos morfológicos que pueden facilitar o retrasar la propagación de la FN y las consecuencias asociadas a los trastornos morfofuncionales provocadas por el tamaño y profundidad de las intervenciones quirúrgicas requeridas por la FN, información relevante para el pronóstico integral a largo plazo del tratamiento de la FN.


Subject(s)
Humans , Female , Middle Aged , Fasciitis, Necrotizing/surgery , Periodontal Abscess/complications , Treatment Outcome , Fasciitis, Necrotizing/etiology , Fasciitis, Necrotizing/microbiology , Fasciitis, Necrotizing/pathology , Recovery of Function , Debridement , Neck/surgery , Neck/pathology
3.
Ear Nose Throat J ; 102(3): NP109-NP113, 2023 Mar.
Article in English | MEDLINE | ID: mdl-33570428

ABSTRACT

IMPORTANCE: Necrotizing fasciitis is a relatively uncommon and potentially life-threatening soft tissue infection, with morbidity and mortality approaching 25% to 35%, even with optimal treatment. The challenge of diagnosis for necrotizing soft tissue infections (NSTIs) is their rarity, with the incidence of approximately 1000 cases annually in the United States. Given the rapid progression of disease and its similar presentation to more benign processes, early and definitive diagnosis is imperative. FINDINGS: Signs and symptoms of NSTIs in the early stages are virtually indistinguishable from those seen with abscesses and cellulitis, making definitive diagnosis difficult. The clinical presentation will depend on the pathogen and its virulence factors which ultimately determine the area and depth of invasion into tissue. There are multiple laboratory value scoring systems that have been developed to support the diagnosis of an NSTI. The scoring system with the highest positive (92%) and negative (96%) predictive value is the laboratory risk indicator for necrotizing fasciitis (LRINEC). The score is determined by 6 serologic markers: C-reactive protein (CRP), total white blood cell (WBC) count, hemoglobin, sodium, creatinine, and glucose. A score ≥ 6 is a relatively specific indicator of necrotizing fasciitis (specificity 83.8%), but a score <6 is not sensitive (59.2%) enough to rule out necrotizing fasciitis. In terms of imaging, computed tomography (CT) imaging, while more sensitive (80%) than plain radiography in detecting abnormalities, is just as nonspecific. Computed tomography imaging of NSTIs demonstrates fascial thickening (with potential fat stranding), edema, subcutaneous gas, and abscess formation. Magnetic resonance imaging (MRI) has demonstrated sensitivity of 100% and specificity of 86%, though MRI may not show early cases of fascial involvement of necrotizing fasciitis. CONCLUSIONS AND RELEVANCE: Necrotizing soft tissue infections are rapidly progressive and potentially fatal infections that require a high index of clinical suspicion to promptly diagnose and aggressive surgical debridement of affected tissue in order to ensure optimal outcomes.Prompt surgical and infectious disease consultation is necessary for the treatment and management of these patients. While imaging is useful for further characterization, it should not delay surgical consultation. Necrotizing soft tissue infection remains a clinical diagnosis, although plain radiography, CT imaging, and ultrasound can provide useful clues. In general, the management of these patients should include rapid diagnosis, using a combination of clinical suspicion, laboratory data (LRINEC score), and imaging (MRI being the recommended imaging modality), prompt infectious disease and surgical consultation, surgical debridement, and delayed reconstruction. Laboratory findings that can more strongly suggest a diagnosis of NSTI include elevated CRP, elevated WBC, low hemoglobin, decreased sodium, and increased creatinine. Imaging findings include fascial thickening (with potential fat stranding), edema, subcutaneous gas, and abscess formation. Broad-spectrum antibiotics should be started in all cases of suspected NSTI. Surgical debridement, however, remains the lynchpin for treatment of cervical necrotizing fasciitis.


Subject(s)
Communicable Diseases , Fasciitis, Necrotizing , Soft Tissue Infections , Humans , Fasciitis, Necrotizing/diagnosis , Fasciitis, Necrotizing/therapy , Fasciitis, Necrotizing/pathology , Soft Tissue Infections/diagnosis , Soft Tissue Infections/therapy , Abscess , Creatinine , Retrospective Studies , Risk Factors , Tomography, X-Ray Computed
4.
Methods Mol Biol ; 2427: 185-200, 2022.
Article in English | MEDLINE | ID: mdl-35619035

ABSTRACT

Group A streptococcus (GAS) necrotizing fasciitis (NF) causes high morbidity and mortality despite prompt intravenous administration of antibiotics, surgical soft-tissue debridement, and supportive treatment in the intensive care unit. Since there is no effective vaccine against GAS infections, a comprehensive understanding of NF pathogenesis is required to design more efficient treatments. To increase our understanding of NF pathogenesis, we need a reliable animal model that mirrors, at least in part, the infectious process in humans. This chapter describes a reliable murine model of human NF that mimics the histopathology observed in humans, namely the destruction of soft tissue, a paucity of infiltrating neutrophils, and the presence of many gram-positive cocci at the center of the infection.


Subject(s)
Fasciitis, Necrotizing , Soft Tissue Infections , Streptococcal Infections , Animals , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Fasciitis, Necrotizing/drug therapy , Fasciitis, Necrotizing/pathology , Mice , Soft Tissue Infections/drug therapy , Streptococcus pyogenes
6.
Medicine (Baltimore) ; 100(51): e28219, 2021 Dec 23.
Article in English | MEDLINE | ID: mdl-34941083

ABSTRACT

ABSTRACT: Necrotizing fasciitis (NF) is a life-threatening soft tissue infection that rapidly progresses and requires urgent surgery and medical therapy. If treatment is delayed, the likelihood of an unfavorable outcome, including death, is significantly increased. The goal of this study was to develop and validate a novel scoring model for predicting mortality in patients with NF. The proposed system is hereafter referred to as the Mortality in Necrotizing Fasciitis (MNF) scoring system. A total of 1503 patients with NF were recruited from 3 provincial hospitals in Thailand during January 2009 to December 2012. Patients were randomly allocated into either the derivation cohort (n = 1192) or the validation cohort (n = 311). Clinical risk factors used to develop the MNF scoring system were determined by logistic regression. Regression coefficients were transformed into item scores, the sum of which reflected the total MNF score. The following 6 clinical predictors were included: female gender; age > 60 years; white blood cell (WBC) ≤5000/mm3; WBC ≥ 35,000/mm3; creatinine ≥ 1.6 mg/dL, and pulse rate > 130/min. Area under the receiver operating characteristic curve (AuROC) analysis showed the MNF scoring system to have moderate power for predicting mortality in patients with NF (AuROC: 76.18%) with good calibration (Hosmer-Lemeshow χ2: 1.01; P = .798). The positive likelihood ratios of mortality in patients with low-risk scores (≤2.5) and high-risk scores (≥7) were 11.30 (95% confidence interval [CI]: 6.16-20.71) and 14.71 (95%CI: 7.39-29.28), sequentially. When used to the validation cohort, the MNF scoring system presented good performance with an AuROC of 74.25%. The proposed MNF scoring system, which includes 6 commonly available and easy-to-use parameters, was shown to be an effective tool for predicting mortality in patients with NF. This validated instrument will help clinicians identify at-risk patients so that early investigations and interventions can be performed that will reduce the mortality rate among patients with NF.


Subject(s)
Fasciitis, Necrotizing/mortality , Risk Assessment/methods , Area Under Curve , Fasciitis, Necrotizing/pathology , Female , Humans , Middle Aged , Predictive Value of Tests , ROC Curve , Retrospective Studies , Risk Factors
9.
Indian J Cancer ; 58(4): 603-607, 2021.
Article in English | MEDLINE | ID: mdl-34975101

ABSTRACT

Necrotizing fasciitis (NF), which is a rare but life-threatening soft tissue infection, can present as a complication of colorectal diseases. The development of NF of the lower extremity secondary to a perforated colorectal tumor has been reported in only a few patients. We present a case of a 68-year-old woman, in which necrotizing soft tissue infection of the left lower extremity was the presenting feature of a perforated rectosigmoid tumor. On examination, there was a tender swelling and edema with palpable crepitus in the left inguinal region and thigh. Computed tomography showed gas within the retroperitoneal tissues, with subcutaneous edema and emphysema extending from the thigh to the ankle. NF was diagnosed, and the patient underwent Hartmann's procedure and fasciotomy with an aggressive debridement of the left thigh and inguinal region. In the case of NF of the lower extremity or abdominal wall without an obvious cutaneous source, an intraabdominal cause should be considered and sought.


Subject(s)
Fasciitis, Necrotizing/etiology , Lower Extremity/pathology , Rectal Neoplasms/complications , Sigmoid Neoplasms/complications , Aged , Fasciitis, Necrotizing/pathology , Female , Humans , Rectal Neoplasms/pathology , Sigmoid Neoplasms/pathology
12.
Adv Exp Med Biol ; 1294: 7-20, 2020.
Article in English | MEDLINE | ID: mdl-33079360

ABSTRACT

All who have contributed in writing this chapter have been patients and parents that have experienced an horrific life event. The horrific disease named necrotising fasciitis has affected our lives for ever. All four stories have explained how easily an everyday infection can develop incredibly quickly into a life-threatening experience. Three stories are expressed from the worn hearts of being a mother, fighting for their child every step of the way. Knowing our children and how they react through pain and illness is felt in each word, sentence, paragraph and even between the lines. Dedicating our unmarkable love and devotion for the child we carried for 9 months. To see them suffer in illness is heart wrenching, but to experience this disease necrotising fasciitis is something else. We must live through every day watching them grow with their scars of debridement, and to support them through further operations, let alone mental scars. Parents show a strength of support like no other and we hope that their lives can be enhanced through the battle they have individually won let alone their family. Robert's story from a patient's perspective is quite different and you will read his courage throughout. We continue to raise awareness through education.


Subject(s)
Fasciitis, Necrotizing/psychology , Patients/psychology , Soft Tissue Infections/psychology , Child , Debridement , Family/psychology , Fasciitis, Necrotizing/pathology , Fasciitis, Necrotizing/therapy , Female , Humans , Soft Tissue Infections/pathology , Soft Tissue Infections/therapy
13.
Infect Immun ; 88(11)2020 10 19.
Article in English | MEDLINE | ID: mdl-32817331

ABSTRACT

Group A Streptococcus (GAS) is a human-specific pathogen and major cause of disease worldwide. The molecular pathogenesis of GAS, like many pathogens, is dependent on the coordinated expression of genes encoding different virulence factors. The control of virulence regulator/sensor (CovRS) two-component system is a major virulence regulator of GAS that has been extensively studied. More recent investigations have also involved regulator of Cov (RocA), a regulatory accessory protein to CovRS. RocA interacts, in some manner, with CovRS; however, the precise molecular mechanism is unknown. Here, we demonstrate that RocA is a membrane protein containing seven transmembrane helices with an extracytoplasmically located N terminus and cytoplasmically located C terminus. For the first time, we demonstrate that RocA directly interacts with itself (RocA) and CovS, but not CovR, in intact cells. Single amino acid replacements along the entire length of RocA disrupt RocA-RocA and RocA-CovS interactions to significantly alter the GAS virulence phenotype as defined by secreted virulence factor activity in vitro and tissue destruction and mortality in vivo In summary, we show that single amino acid replacements in a regulatory accessory protein can affect protein-protein interactions to significantly alter the virulence of a major human pathogen.


Subject(s)
Bacterial Proteins/genetics , Fasciitis, Necrotizing/microbiology , Histidine Kinase/genetics , Myositis/microbiology , Repressor Proteins/genetics , Streptococcal Infections/microbiology , Streptococcus pyogenes/genetics , Trans-Activators/genetics , Amino Acid Sequence , Amino Acid Substitution , Animals , Bacterial Proteins/chemistry , Bacterial Proteins/metabolism , Binding Sites , Cloning, Molecular , Escherichia coli/genetics , Escherichia coli/metabolism , Fasciitis, Necrotizing/metabolism , Fasciitis, Necrotizing/mortality , Fasciitis, Necrotizing/pathology , Female , Gene Expression , Gene Expression Regulation, Bacterial , Genetic Vectors/chemistry , Genetic Vectors/metabolism , Histidine Kinase/chemistry , Histidine Kinase/metabolism , Humans , Mice , Mutation , Myositis/metabolism , Myositis/mortality , Myositis/pathology , Protein Binding , Protein Interaction Domains and Motifs , Protein Structure, Secondary , Repressor Proteins/chemistry , Repressor Proteins/metabolism , Streptococcal Infections/metabolism , Streptococcal Infections/mortality , Streptococcal Infections/pathology , Streptococcus pyogenes/growth & development , Streptococcus pyogenes/metabolism , Streptococcus pyogenes/pathogenicity , Survival Analysis , Trans-Activators/chemistry , Trans-Activators/metabolism , Virulence
15.
Am J Otolaryngol ; 41(6): 102613, 2020.
Article in English | MEDLINE | ID: mdl-32599441

ABSTRACT

PURPOSE: Cervical Necrotizing fasciitis (CNF) has been reported as an unusual rapidly progressive, life-threatening, inflammatory disease that is known to affect predominately immunocompromised patients. Few case reports have been sporadically published involving immunocompetent adults. This is the first study presents a series of immunocompetent CNF patients. MATERIALS AND METHODS: A retrospective chart review study was performed on immunocompetent adults with CNF from January 2003 to December 2019. The diagnosis was histologically confirmed. We analyzed epidemiological, clinical, laboratory and imaging findings and discussed them along with the treatment plan. RESULTS: A total of eleven adult patients were included in the study. The average age was 43 years, ranging from 17 to 62 years. The average hospitalization time was 28 days, ranging from 10 to 129 days. All patients presented with cervical erythema and odynophagia. The causative factors are known in nine patients. Tissue cultures demonstrated mixed flora in six patients. Seven underwent a temporary tracheostomy. Wide neck exploration incisions were performed in all patients as the diagnosis was established after imaging findings. In nine cases the anterior-upper mediastinum was affected but only in two patients extension of the surgical planes to the mediastinum was performed. Four patients developed polyserositis. Nine patients survived and two developed multiorgan failure and died. CONCLUSION: There seem to be no differences between immunocompetent and immunocompromised CNF patients, in regards to clinical, imaging and laboratory findings as well as their treatment plan.


Subject(s)
Fasciitis, Necrotizing/diagnosis , Fasciitis, Necrotizing/surgery , Immunocompetence , Neck , Adolescent , Adult , Debridement , Fasciitis, Necrotizing/mortality , Fasciitis, Necrotizing/pathology , Female , Humans , Immunocompromised Host , Length of Stay , Male , Middle Aged , Retrospective Studies , Survival Rate , Tracheostomy , Treatment Outcome , Young Adult
16.
Sci Rep ; 10(1): 7716, 2020 05 07.
Article in English | MEDLINE | ID: mdl-32382057

ABSTRACT

Necrotizing fasciitis (NF) of the limbs caused by Aeromonas species is an extremely rare and life-threatening skin and soft tissue infection. The purpose of this study was to evaluate the specific characteristics and the independent predictors of mortality in patients with Aeromonas NF. Sixty-eight patients were retrospectively reviewed over an 18-year period. Differences in mortality, demographics data, comorbidities, symptoms and signs, laboratory findings, microbiological analysis, empiric antibiotics treatment and clinical outcomes were compared between the non-survival and the survival groups. Twenty patients died with the mortality rate of 29.4%. The non-survival group revealed significant differences in bacteremia, monomicrobial infection, cephalosporins resistance, initial ineffective empiric antibiotics usage, chronic kidney disease, chronic hepatic dysfunction, tachypnea, shock, hemorrhagic bullae, skin necrosis, leukopenia, band polymorphonuclear neutrophils >10%, anemia, and thrombocytopenia. The multivariate analysis identified four variables predicting mortality: bloodstream infection, shock, skin necrosis, and initial ineffective empirical antimicrobial usage against Aeromonas. NF caused by Aeromonas spp. revealed high mortality rates, even through aggressive surgical debridement and antibacterial therapies. Identifying those independent predictors, such as bacteremia, shock, progressive skin necrosis, monomicrobial infection, and application of the effective antimicrobial agents against Aeromonas under the supervision of infectious doctors, may improve clinical outcomes.


Subject(s)
Aeromonas/pathogenicity , Bacteremia/mortality , Fasciitis, Necrotizing/mortality , Soft Tissue Infections/mortality , Aged , Bacteremia/microbiology , Bacteremia/pathology , Comorbidity , Extremities/microbiology , Extremities/pathology , Fasciitis, Necrotizing/microbiology , Fasciitis, Necrotizing/pathology , Female , Humans , Male , Middle Aged , Retrospective Studies , Risk Factors , Skin/microbiology , Skin/pathology , Soft Tissue Infections/microbiology , Soft Tissue Infections/pathology
17.
Article in Chinese | MEDLINE | ID: mdl-32306633

ABSTRACT

Objective: To explore the clinical experience in care for deep neck infection (DNI) and to analyze the factors influencing surgical treatment outcome. Methods: A retrospective analysis was conducted on 61 patients with DNI admitted to the Department of Otorhinolaryngology Head and Neck Surgery of Yantai Yuhuangding Hospital from March 2013 to April 2019, including 33 males and 28 females, aged from 6 months to 81 years with a median age of 49 years. Patients were divided into two groups, 31 cases with localized infection (neck abscess) in Group A and 30 cases with diffuse infection (neck necrotizing fasciitis) in Group B. Patients in two groups were compared for sex, age, hospital stay, diabetes, tracheostomy, drainage methods, mediastinal infection, and pathogenic bacteria. The influence of different drainage methods on hospital stay in Group A was analyzed. SPSS 25.0 software was used for statistical analysis. Results: Of the 61 patients, 45 patients underwent surgical incision and drainage (21 cases in Group A and 24 cases in Group B), 23 patients underwent ultrasound-guided fine needle aspiration (UG-FNA) and catheter drainage (10 cases in Group A and 13 cases in Group B), and 7 patients in Group B were treated with both drainage methods. Pathogens were cultured in 31 cases (50.82%). There were significant differences in hospital stay, drainage method and mediastinal infection (χ(2) values were 26.890, 8.687 and 6.035, respectively, P<0.05), but no significant difference was found in sex, age, diabetes, tracheotomy and pathogenic bacteria (χ(2) values were 0.157, 3.685, 2.434, 3.631 and 0.807, respectively, P>0.05) between the two groups. There was no significant difference in hospital stay between two drainage methods in patients in Group A (χ(2)=1.560, P>0.05). Conclusions: There were significant differences in hospital stay, drainage method and mediastinal infection between patients with localized infection and diffuse infection, as diffuse infection is often associated with serious complications. UG-FNA and catheter drainage is an optional method for the treatment of localized infection, with minimal invasion and no influence on hospital stay.


Subject(s)
Abscess/microbiology , Bacterial Infections/pathology , Fasciitis, Necrotizing/microbiology , Mediastinitis/microbiology , Neck/microbiology , Neck/pathology , Abscess/pathology , Abscess/therapy , Adolescent , Adult , Aged , Aged, 80 and over , Bacterial Infections/therapy , Child , Child, Preschool , Drainage , Fasciitis, Necrotizing/pathology , Fasciitis, Necrotizing/therapy , Female , Humans , Infant , Length of Stay , Male , Mediastinitis/pathology , Mediastinitis/therapy , Middle Aged , Retrospective Studies , Young Adult
18.
PLoS One ; 15(3): e0229064, 2020.
Article in English | MEDLINE | ID: mdl-32214338

ABSTRACT

Streptococcus pyogenes is a strict human pathogen responsible for more than 700 million infections annually worldwide. Strains of serotype M28 S. pyogenes are typically among the five more abundant types causing invasive infections and pharyngitis in adults and children. Type M28 strains also have an unusual propensity to cause puerperal sepsis and neonatal disease. We recently discovered that a one-nucleotide indel in an intergenic homopolymeric tract located between genes Spy1336/R28 and Spy1337 altered virulence in a mouse model of infection. In the present study, we analyzed size variation in this homopolymeric tract and determined the extent of heterogeneity in the number of tandemly-repeated 79-amino acid domains in the coding region of Spy1336/R28 in large samples of strains recovered from humans with invasive infections. Both repeat sequence elements are highly polymorphic in natural populations of M28 strains. Variation in the homopolymeric tract results in (i) changes in transcript levels of Spy1336/R28 and Spy1337 in vitro, (ii) differences in virulence in a mouse model of necrotizing myositis, and (iii) global transcriptome changes as shown by RNAseq analysis of isogenic mutant strains. Variation in the number of tandem repeats in the coding sequence of Spy1336/R28 is responsible for size variation of R28 protein in natural populations. Isogenic mutant strains in which genes encoding R28 or transcriptional regulator Spy1337 are inactivated are significantly less virulent in a nonhuman primate model of necrotizing myositis. Our findings provide impetus for additional studies addressing the role of R28 and Spy1337 variation in pathogen-host interactions.


Subject(s)
Bacterial Proteins/genetics , Fasciitis, Necrotizing/microbiology , Streptococcal Infections/microbiology , Streptococcus pyogenes/genetics , Streptococcus pyogenes/isolation & purification , Virulence/genetics , Animals , Disease Models, Animal , Fasciitis, Necrotizing/pathology , Gene Expression Regulation, Bacterial , Genetic Heterogeneity , Humans , Mice , Polymorphism, Genetic , Streptococcal Infections/pathology , Transcriptome , Virulence Factors/genetics
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