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1.
Emerg Infect Dis ; 29(4): 848-850, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-36918374

RESUMEN

We retrospectively screened oropharyngeal and rectal swab samples originally collected in California, USA, for Chlamydia trachomatis and Neisseria gonorrhoeae testing for the presence of monkeypox virus DNA. Among 206 patients screened, 17 (8%) had samples with detectable viral DNA. Monkeypox virus testing from mucosal sites should be considered for at-risk patients.


Asunto(s)
Infecciones por Chlamydia , Gonorrea , Mpox , Humanos , California/epidemiología , Infecciones por Chlamydia/diagnóstico , Infecciones por Chlamydia/epidemiología , Chlamydia trachomatis/genética , Chlamydia trachomatis/aislamiento & purificación , ADN , Gonorrea/diagnóstico , Monkeypox virus/genética , Monkeypox virus/aislamiento & purificación , Neisseria gonorrhoeae/genética , Neisseria gonorrhoeae/aislamiento & purificación , Estudios Retrospectivos , Mpox/diagnóstico
2.
J Clin Microbiol ; 61(11): e0077523, 2023 11 21.
Artículo en Inglés | MEDLINE | ID: mdl-37843251

RESUMEN

The QuantiFERON-TB Gold (QFT) is routinely utilized in North American health systems to detect a cellular immune response to Mycobacterium tuberculosis antigens in symptomatic and asymptomatic patients. The sensitivity of QFT in tuberculosis (TB) patients with comorbidities is not well established and the specificity of QFT in patients with nontuberculous mycobacteria (NTM) infections is incompletely understood. Between 2012 and 2023, all patients with culture-positive TB and patients with NTM infection per the expert diagnostic guidelines or biopsy-proven NTM infection who had a concurrent QFT test were included in this study. The sensitivity and specificity of QFT were measured in TB and NTM patients, respectively. In 109 patients with active TB, the overall sensitivity of QFT was 78.0% (85/109; 95% CI: 70.1, 85.7). The sensitivity was 86.0% (49/57; 95% CI: 76.6, 94.8) and 69.2% (36/52; 95% CI: 56.7, 81.8) in immunocompetent and immunocompromised patients, respectively. The overall specificity of QFT in 88 patients with NTM infection was 76.1% (67/88; 95% CI: 67.2, 85.0). After the exclusion of 17 NTM patients with risk factors for latent TB infection, the specificity was 94.4% (67/71; 95% CI: 89.1, 99.7). Two patients had NTM species known to cross-react with QFT. In two NTM patients infected with species (Mycobacterium intracellulare subsp. intracellulare and Mycobacterium intracellulare subsp. chimaera) not known to cross-react, whole genome sequencing did not detect ESAT-6 or CFP-10. In Northern California, the QFT assay demonstrated moderately low to moderately high sensitivity in TB patients and very high specificity in NTM patients, thus ruling out concerns for cross-reactivity with NTM.


Asunto(s)
Infecciones por Mycobacterium no Tuberculosas , Mycobacterium tuberculosis , Tuberculosis , Humanos , Tuberculosis/diagnóstico , Tuberculosis/microbiología , Infecciones por Mycobacterium no Tuberculosas/diagnóstico , Infecciones por Mycobacterium no Tuberculosas/epidemiología , Comorbilidad , Sensibilidad y Especificidad , Factores de Riesgo , Mycobacterium tuberculosis/genética , Prueba de Tuberculina , Ensayos de Liberación de Interferón gamma
3.
BMC Microbiol ; 22(1): 23, 2022 01 13.
Artículo en Inglés | MEDLINE | ID: mdl-35026981

RESUMEN

BACKGROUND: Streptococcus agalactiae or Group B Streptococcus (GBS) is an encapsulated gram-positive bacterial pathobiont that commonly colonizes the lower gastrointestinal tract and reproductive tract of human hosts. This bacterium can infect the gravid reproductive tract and cause invasive infections of pregnant patients and neonates. Upon colonizing the reproductive tract, the bacterial cell is presented with numerous nutritional challenges imposed by the host. One strategy employed by the host innate immune system is intoxication of bacterial invaders with certain transition metals such as zinc. METHODOLOGY: Previous work has demonstrated that GBS must employ elegant strategies to circumnavigate zinc stress in order to survive in the vertebrate host. We assessed 30 strains of GBS from diverse isolation sources, capsular serotypes, and sequence types for susceptibility or resistance to zinc intoxication. RESULTS: Invasive strains, such as those isolated from early onset disease manifestations of GBS infection were significantly less susceptible to zinc toxicity than colonizing strains isolated from rectovaginal swabs of pregnant patients. Additionally, capsular type III (cpsIII) strains and the ST-17 and ST-19 strains exhibited the greatest resilience to zinc stress, whereas ST-1 and ST-12 strains as well as those possessing capsular type Ib (cpsIb) were more sensitive to zinc intoxication. Thus, this study demonstrates that the transition metal zinc possesses antimicrobial properties against a wide range of GBS strains, with isolation source, capsular serotype, and sequence type contributing to susceptibility or resistance to zinc stress.


Asunto(s)
Antibacterianos/farmacología , Cloruros/farmacocinética , Serogrupo , Streptococcus agalactiae/efectos de los fármacos , Streptococcus agalactiae/genética , Compuestos de Zinc/farmacocinética , Antibacterianos/metabolismo , Cápsulas Bacterianas/clasificación , Cápsulas Bacterianas/efectos de los fármacos , Cloruros/metabolismo , Femenino , Humanos , Recién Nacido , Pruebas de Sensibilidad Microbiana , Embarazo , Serotipificación , Infecciones Estreptocócicas/sangre , Infecciones Estreptocócicas/tratamiento farmacológico , Infecciones Estreptocócicas/microbiología , Streptococcus agalactiae/clasificación , Streptococcus agalactiae/crecimiento & desarrollo , Vagina/efectos de los fármacos , Vagina/microbiología , Compuestos de Zinc/metabolismo
4.
Bioorg Med Chem ; 74: 117037, 2022 11 15.
Artículo en Inglés | MEDLINE | ID: mdl-36215812

RESUMEN

Adverse pregnancy outcomes affect 54 million people globally per year, with at least 50% of these attributed to infection during gestation. These include inflammation of the membranes surrounding the growing fetus (chorioamnionitis), preterm prelabor rupture of membranes (PPROM), preterm birth (PTB), early-onset disease (EOD) and late-onset disease (LOD), neonatal and maternal sepsis, and maternal or fetal demise. Although universal screening and implementation of intrapartum antibiotic prophylaxis (IAP) has improved EOD outcomes, these interventions have not reduced the incidences of LOD or complications occurring early on during pregnancy such as PPROM and PTB. Thus, novel therapies are needed to prevent adverse pregnancy outcomes and to ameliorate disease risk in vulnerable populations. Lactoferrin has recently been explored as a potential therapeutic as it demonstrates strong antimicrobial and anti-biofilm activity. Lactoferrin is a glycoprotein capable of iron chelation found in a variety of human tissues and is produced in high concentrations in human breast milk. In recent studies, lactoferrin has shown promise inhibiting growth and biofilm formation of streptococcal species, including Group B Streptococcus (GBS), a prominent perinatal pathogen. Understanding the interactions between lactoferrin and GBS could elucidate a novel treatment strategy for adverse pregnancy outcomes caused by GBS infection.


Asunto(s)
Nacimiento Prematuro , Infecciones Estreptocócicas , Embarazo , Femenino , Recién Nacido , Humanos , Lactoferrina/farmacología , Lactoferrina/uso terapéutico , Nacimiento Prematuro/tratamiento farmacológico , Factores de Riesgo , Streptococcus agalactiae , Infecciones Estreptocócicas/prevención & control
5.
Chembiochem ; 22(12): 2124-2133, 2021 06 15.
Artículo en Inglés | MEDLINE | ID: mdl-33755306

RESUMEN

Group B Streptococcus (GBS) is an encapsulated Gram-positive human pathogen that causes invasive infections in pregnant hosts and neonates, as well as immunocompromised individuals. Colonization of the human host requires the ability to adhere to mucosal surfaces and circumnavigate the nutritional challenges and antimicrobial defenses associated with the innate immune response. Biofilm formation is a critical process to facilitate GBS survival and establishment of a replicative niche in the vertebrate host. Previous work has shown that the host responds to GBS infection by producing the innate antimicrobial glycoprotein lactoferrin, which has been implicated in repressing bacterial growth and biofilm formation. Additionally, lactoferrin is highly abundant in human breast milk and could serve a protective role against invasive microbial pathogens. This study demonstrates that human breast milk lactoferrin has antimicrobial and anti-biofilm activity against GBS and inhibits its adherence to human gestational membranes. Together, these results indicate that human milk lactoferrin could be used as a prebiotic chemotherapeutic strategy to limit the impact of bacterial adherence and biofilm formation on GBS-associated disease outcomes.


Asunto(s)
Antibacterianos/farmacología , Lactoferrina/inmunología , Leche Humana/química , Streptococcus agalactiae/efectos de los fármacos , Antibacterianos/química , Adhesión Bacteriana/efectos de los fármacos , Adhesión Bacteriana/inmunología , Biopelículas/efectos de los fármacos , Femenino , Humanos , Inmunidad Innata/efectos de los fármacos , Inmunidad Innata/inmunología , Lactoferrina/química , Pruebas de Sensibilidad Microbiana , Streptococcus agalactiae/inmunología
6.
Chembiochem ; 22(18): 2783-2790, 2021 09 14.
Artículo en Inglés | MEDLINE | ID: mdl-34169626

RESUMEN

Chronic infection with Helicobacter pylori increases risk of gastric diseases including gastric cancer. Despite development of a robust immune response, H. pylori persists in the gastric niche. Progression of gastric inflammation to serious disease outcomes is associated with infection with H. pylori strains which encode the cag Type IV Secretion System (cag T4SS). The cag T4SS is responsible for translocating the oncogenic protein CagA into host cells and inducing pro-inflammatory and carcinogenic signaling cascades. Our previous work demonstrated that nutrient iron modulates the activity of the T4SS and biogenesis of T4SS pili. In response to H. pylori infection, the host produces a variety of antimicrobial molecules, including the iron-binding glycoprotein, lactoferrin. Our work shows that apo-lactoferrin exerts antimicrobial activity against H. pylori under iron-limited conditions, while holo-lactoferrin enhances bacterial growth. Culturing H. pylori in the presence of holo-lactoferrin prior to co-culture with gastric epithelial cells, results in repression of the cag T4SS activity. Concomitantly, a decrease in biogenesis of cag T4SS pili at the host-pathogen interface was observed under these culture conditions by high-resolution electron microscopy analyses. Taken together, these results indicate that acquisition of alternate sources of nutrient iron plays a role in regulating the pro-inflammatory activity of a bacterial secretion system and present novel therapeutic targets for the treatment of H. pylori-related disease.


Asunto(s)
Helicobacter pylori/efectos de los fármacos , Lactoferrina/farmacología , Sistemas de Secreción Tipo IV/metabolismo , Animales , Modelos Animales de Enfermedad , Células Epiteliales/citología , Células Epiteliales/efectos de los fármacos , Células Epiteliales/metabolismo , Mucosa Gástrica/citología , Mucosa Gástrica/metabolismo , Gerbillinae , Infecciones por Helicobacter/tratamiento farmacológico , Infecciones por Helicobacter/microbiología , Helicobacter pylori/metabolismo , Inmunidad Innata , Interleucina-8/metabolismo , Hierro/metabolismo , Lactoferrina/química , Lactoferrina/metabolismo , Lactoferrina/uso terapéutico , Isoformas de Proteínas/química , Isoformas de Proteínas/metabolismo , Isoformas de Proteínas/farmacología , Isoformas de Proteínas/uso terapéutico , Sistemas de Secreción Tipo IV/antagonistas & inhibidores
7.
BMC Microbiol ; 21(1): 21, 2021 01 09.
Artículo en Inglés | MEDLINE | ID: mdl-33422000

RESUMEN

BACKGROUND: Acinetobacter baumannii is a gram-negative bacterium which causes opportunistic infections in immunocompromised hosts. Genome plasticity has given rise to a wide range of strain variation with respect to antimicrobial resistance profiles and expression of virulence factors which lead to altered phenotypes associated with pathogenesis. The purpose of this study was to analyze clinical strains of A. baumannii for phenotypic variation that might correlate with virulence phenotypes, antimicrobial resistance patterns, or strain isolation source. We hypothesized that individual strain virulence phenotypes might be associated with anatomical site of isolation or alterations in susceptibility to antimicrobial interventions. METHODOLOGY: A cohort of 17 clinical isolates of A. baumannii isolated from diverse anatomical sites were evaluated to ascertain phenotypic patterns including biofilm formation, hemolysis, motility, and antimicrobial resistance. Antibiotic susceptibility/resistance to ampicillin-sulbactam, amikacin, ceftriaxone, ceftazidime, cefotaxime, ciprofloxacin, cefepime, gentamicin, levofloxacin, meropenem, piperacillin, trimethoprim-sulfamethoxazole, ticarcillin- K clavulanate, tetracyclin, and tobramycin was determined. RESULTS: Antibiotic resistance was prevalent in many strains including resistance to ampicillin-sulbactam, amikacin, ceftriaxone, ceftazidime, cefotaxime, ciprofloxacin, cefepime, gentamicin, levofloxacin, meropenem, piperacillin, trimethoprim-sulfamethoxazole, ticarcillin- K clavulanate, tetracyclin, and tobramycin. All strains tested induced hemolysis on agar plate detection assays. Wound-isolated strains of A. baumannii exhibited higher motility than strains isolated from blood, urine or Foley catheter, or sputum/bronchial wash. A. baumannii strains isolated from patient blood samples formed significantly more biofilm than isolates from wounds, sputum or bronchial wash samples. An inverse relationship between motility and biofilm formation was observed in the cohort of 17 clinical isolates of A. baumannii tested in this study. Motility was also inversely correlated with induction of hemolysis. An inverse correlation was observed between hemolysis and resistance to ticarcillin-k clavulanate, meropenem, and piperacillin. An inverse correlation was also observed between motility and resistance to ampicillin-sulbactam, ceftriaxone, ceftoxamine, ceftazidime, ciprofloxacin, or levofloxacin. CONCLUSIONS: Strain dependent variations in biofilm and motility are associated with anatomical site of isolation. Biofilm and hemolysis production both have an inverse association with motility in the cohort of strains utilized in this study, and motility and hemolysis were inversely correlated with resistance to numerous antibiotics.


Asunto(s)
Infecciones por Acinetobacter/microbiología , Acinetobacter baumannii/patogenicidad , Antibacterianos/farmacología , Farmacorresistencia Bacteriana Múltiple , Heridas y Lesiones/microbiología , Infecciones por Acinetobacter/sangre , Acinetobacter baumannii/efectos de los fármacos , Acinetobacter baumannii/genética , Acinetobacter baumannii/aislamiento & purificación , Adaptación Fisiológica , Carbapenémicos/farmacología , Catéteres/microbiología , Humanos , Pruebas de Sensibilidad Microbiana , Fenotipo , Piperacilina/farmacología , Esputo/microbiología , Tennessee , Orina/microbiología
8.
Hum Reprod ; 34(4): 702-714, 2019 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-30789661

RESUMEN

STUDY QUESTION: Does the uterine vasculature play a localized role in promoting stromal cell decidualization in the human endometrium? SUMMARY ANSWER: Our study demonstrated that hemodynamic forces induced secretion of specific endothelial cell-derived prostanoids that enhanced endometrial perivascular decidualization via a paracrine mechanism. WHAT IS KNOWN ALREADY: Differentiation of stromal cell fibroblasts into the specialized decidua of the placenta is a progesterone-dependent process; however, histologically, it has long been noted that the first morphological signs of decidualization appear in the perivascular stroma. These observations suggest that the human endometrial vasculature plays an active role in promoting stromal differentiation. STUDY DESIGN, SIZE, DURATION: Primary human endometrial stromal cells were co-cultured for 14 days with primary uterine microvascular endothelial cells within a microfluidic Organ-on-Chip model of the endometrium. PARTICIPANTS/MATERIALS, SETTING, METHODS: Cultures were maintained with estradiol and a progestin, with or without continuous laminar perfusion to mimic hemodynamic forces derived from the blood flow. Some cultures additionally received exogenous agonist-mediated challenges. Decidualization in the microfluidic model was assessed morphologically and biochemically. ELISA was used to examine the culture effluent for expression of decidualization markers and prostaglandins. Immunofluorescence was used to monitor cyclooxygenase-2 expression in association with decidualization. MAIN RESULTS AND THE ROLE OF CHANCE: A significantly enhanced stromal decidualization response was observed in the co-cultures when the endothelial cells were stimulated with hemodynamic forces (e.g. laminar shear stress) derived from controlled microfluidic perfusion (<0.001). Furthermore, the enhanced progestin-driven stromal differentiation was mediated via cyclooxygenase-2 and the paracrine action of prostaglandin E2 and prostacyclin. Altogether, these translational findings indicate that the vascular endothelium plays a key physiologic role during the early events of perivascular decidualization in the human endometrium. LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: This report is largely an in vitro study. Although we were able to experimentally mimic hemodynamic forces in our microfluidic model, we have not yet determined the contribution of additional cell types to the decidualization process or determined the precise physiological rates of shear stress that the microvasculature of the endometrium undergoes in vivo. WIDER IMPLICATIONS OF THE FINDINGS: Identification of specific endothelial-derived prostaglandins and their role during endometrial reproductive processes may have clinical utility as therapeutic targets for reproductive disorders such as infertility, endometriosis, adenomyosis, pre-eclampsia and poor pregnancy outcomes. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the Veterans Affairs (I01 BX002853), the Bill and Melinda Gates Foundation Grand Challenges Exploration (OPP1159411), the Environmental Toxicology Training Grant (NIH T32 ES007028) and the Environmental Protection Agency STAR Center Grant (83573601). CONFLICT OF INTEREST: The authors report no conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.


Asunto(s)
Decidua/irrigación sanguínea , Decidua/metabolismo , Dinoprostona/metabolismo , Células Endoteliales/metabolismo , Epoprostenol/metabolismo , Hemodinámica/fisiología , Microfluídica/instrumentación , Adolescente , Adulto , Arteriolas/metabolismo , Diferenciación Celular/fisiología , Células Cultivadas , Técnicas de Cocultivo , Ciclooxigenasa 2/metabolismo , Decidua/citología , Femenino , Fibroblastos/metabolismo , Humanos , Microfluídica/métodos , Persona de Mediana Edad , Comunicación Paracrina/fisiología , Células del Estroma/metabolismo , Adulto Joven
10.
BMC Public Health ; 16: 442, 2016 05 26.
Artículo en Inglés | MEDLINE | ID: mdl-27230281

RESUMEN

BACKGROUND: Alcohol-related harm is a major global health issue, and controls on alcohol marketing are one intervention utilized by governments. This study investigated the use of Google Street View (GSV) as a novel research method for collecting alcohol-related data in the urban environment. METHODS: The efficacy of GSV and on-street observation by observer teams was compared by surveying 400 m stretches of 12 streets in Wellington, the capital city of New Zealand. Data on alcohol sale, alcohol-related advertising, health promotion materials, regulatory information and visible alcohol consumption were collected. RESULTS: A total of 403 retailers with evidence of alcohol sales and 1161 items of alcohol-related communication were identified in on-street observation. Of the latter, 1028 items (89 %) were for alcohol marketing and 133 (11 %) were for alcohol-related health promotion and alcohol regulation. GSV was found to be a less sensitive tool than on-street observation with only 50 % of the alcohol venues identified and 52 % of the venue-associated brand marketing identified. A high degree of inter-observer reliability was generally found between pairs of observers e.g., for the detection of alcohol retail venues the intra-class correlation coefficient (ICC) was 0.93 (95 % CI: 0.78 to 0.98) for on-street observation and 0.85 (95 % CI: 0.49 to 0.96) for using GSV. CONCLUSIONS: GSV does not seem suitable for the comprehensive study of the influences on alcohol consumption in the urban streetscape. However, it may still have value for large, static objects in the environment and be more time efficient than traditional on-street observation measures, especially when used to collect data across a wide geographical area. Furthermore, GSV might become a more useful research tool in settings with better image quality (such as more 'footpath views') and with more regularly updated GSV imagery.


Asunto(s)
Consumo de Bebidas Alcohólicas/prevención & control , Planificación Ambiental , Sistemas de Información Geográfica , Mercadotecnía , Promoción de la Salud , Humanos , Nueva Zelanda , Variaciones Dependientes del Observador , Reproducibilidad de los Resultados , Salud Urbana
11.
Clin Lab Med ; 44(1): 13-21, 2024 03.
Artículo en Inglés | MEDLINE | ID: mdl-38280794

RESUMEN

Though testing for infectious diseases has long been performed in traditional clincial laboratory settings, more widespread availability of waived testing is expanding accessibility of patients to rapid test results. This is being further expanded to home testing. Nevertheless, with this greater democratization and availability of clinical testing there are important limitations that need to be balanced. In this article, we review the current test landscape for infectious diseases waived testing and opportunities for assuring optimal quality testing.


Asunto(s)
Enfermedades Transmisibles , Laboratorios Clínicos , Humanos , Técnicas de Laboratorio Clínico , Enfermedades Transmisibles/diagnóstico , Laboratorios
12.
IDCases ; 33: e01881, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37680215

RESUMEN

As part of an epidemiologic survey, we screened remnant samples collected for STI testing for mpox virus. We identified two cases of presumed MPXV infection in pregnant, heterosexual cisgender women. Here, we describe their pregnancy and birth outcomes. Both patients required induction of labor and experienced labor complicated by chorioamnionitis.

13.
ACS Cent Sci ; 9(9): 1737-1749, 2023 Sep 27.
Artículo en Inglés | MEDLINE | ID: mdl-37780357

RESUMEN

Preterm birth affects nearly 10% of all pregnancies in the United States, with 40% of those due, in part, to infections. Streptococcus agalactiae (Group B Streptococcus, GBS) is one of the most common perinatal pathogens responsible for these infections. Current therapeutic techniques aimed to ameliorate invasive GBS infections are less than desirable and can result in complications in both the neonate and the mother. To this end, the need for novel therapeutic options is urgent. Human milk oligosaccharides (HMOs), an integral component of human breast milk, have been previously shown to possess antiadhesive and antimicrobial properties. To interrogate these characteristics, we examined HMO-mediated outcomes in both in vivo and ex vivo models of GBS infection utilizing a murine model of ascending GBS infection, an EpiVaginal human organoid tissue model, and ex vivo human gestational membranes. Supplementation of HMOs resulted in diminished adverse pregnancy outcomes, decreased GBS adherence to gestational tissues, decreased colonization within the reproductive tract, and reduced proinflammatory immune responses to GBS infection. Taken together, these results highlight the potential of HMOs as promising therapeutic interventions in perinatal health.

14.
J Clin Virol ; 164: 105493, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-37220710

RESUMEN

BACKGROUND: Despite the sharp increase in mpox (formerly monkeypox) incidence and the wide geographic spread of mpox during the 2022 outbreak, the community prevalence of infection remains poorly characterized. This study is a retrospective epidemiologic survey to estimate mpox prevalence. METHODS: Samples obtained for sexually transmitted infection (STI) testing from April to September 2022 in the public hospital and clinic system of San Mateo County, California were screened for mpox virus (MPXV) using polymerase chain reaction. RESULTS: 16/1,848 samples from 11/1,645 individuals were positive for MPXV by qPCR. 4/11 individuals with positive MPXV testing were cisgender women, 2 of whom were pregnant at the time of sample collection. Both deliveries were complicated by chorioamnionitis. Anorectal and oropharyngeal samples were the most likely to be positive for MPXV (4/60 anorectal samples and 4/66 oropharyngeal samples compared with 5/1,264 urine samples and 3/445 vaginal samples). CONCLUSIONS: Our study is one of the first epidemiologic surveys for MPXV infection outside of sexual health/STI clinic settings. Relatively high rates of MPXV from oropharyngeal and anorectal samples reinforces the importance of MPXV testing at various anatomic sites, particularly if patients are presenting with non-lesional symptoms (pharyngitis, proctitis). However, the United States Food and Drug Administration (FDA) has not yet authorized non-lesional MPXV testing. The identification of MPXV in women in our cohort suggests that the rates of mpox in women may have previously been underestimated and highlights the risk of pregnancy complications associated with mpox.


Asunto(s)
Mpox , Embarazo , Humanos , Femenino , Prevalencia , Estudios Retrospectivos , Instituciones de Atención Ambulatoria , California/epidemiología , Monkeypox virus
15.
ACS Infect Dis ; 9(12): 2401-2408, 2023 Dec 08.
Artículo en Inglés | MEDLINE | ID: mdl-37955242

RESUMEN

Exposure to environmental toxicants (such as dioxins) has been epidemiologically linked to adverse reproductive health outcomes, including placental inflammation and preterm birth. However, the molecular underpinnings that govern these outcomes in gravid reproductive tissues remain largely unclear. Placental macrophages (also known as Hofbauer cells) are crucial innate immune cells that defend the gravid reproductive tract and help promote maternal-fetal tolerance. We hypothesized that exposure to environmental toxicants such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) could alter placental macrophage responses to inflammatory insults such as infection. To test this, placental macrophages were cultured in the presence or absence of TCDD and then infected with the perinatal pathogen Group B Streptococcus (GBS). Our results indicate that TCDD is lethal to placental macrophages at and above a 5 nM concentration and that sublethal dioxin exposure inhibits phagocytosis and cytokine production. Taken together, these results indicate that TCDD paralyzes placental macrophage responses to bacterial infection.


Asunto(s)
Dioxinas , Dibenzodioxinas Policloradas , Nacimiento Prematuro , Humanos , Embarazo , Recién Nacido , Femenino , Placenta , Dibenzodioxinas Policloradas/toxicidad , Macrófagos
16.
ACS Infect Dis ; 8(12): 2405-2412, 2022 12 09.
Artículo en Inglés | MEDLINE | ID: mdl-36445344

RESUMEN

Group B Streptococcus (GBS) is a gram-positive bacterium that can cause invasive infections in immunocompromised, elderly, pregnant, or neonatal patients. The invertebrate model, Galleria mellonella, has emerged as an effective tool to study GBS-host interactions; specifically, those conserved within the innate arm of the immune system. We sought to determine the role of metal homeostasis functions in GBS infections of G. mellonella larvae and to validate this model as a tool to study GBS-host interactions. Our results indicate that wild-type GBS infects G. mellonella in a dose-dependent manner, replicates in the invertebrate host, induces larval melanization and larval killing. These results were significantly abrogated in cohorts of larvae infected with the isogenic cadD deletion mutant. Additionally, complementation restored GBS-dependent infection, bacterial burden, larval melanization, and killing to wild-type levels. Together, these results indicate that the G. mellonella model is a useful tool for studying GBS pathogenesis.


Asunto(s)
Streptococcus agalactiae , Recién Nacido , Humanos , Anciano
17.
mBio ; 13(6): e0287022, 2022 12 20.
Artículo en Inglés | MEDLINE | ID: mdl-36409087

RESUMEN

Streptococcus agalactiae, also known as group B Streptococcus (GBS), is a Gram-positive encapsulated bacterium that colonizes the gastrointestinal tract of 30 to 50% of humans. GBS causes invasive infection during pregnancy that can lead to chorioamnionitis, funisitis, preterm prelabor rupture of membranes (PPROM), preterm birth, neonatal sepsis, and maternal and fetal demise. Upon infecting the host, GBS encounters sentinel innate immune cells, such as macrophages, within reproductive tissues. Once phagocytosed by macrophages, GBS upregulates the expression of the gene npx, which encodes an NADH peroxidase. GBS mutants with an npx deletion (Δnpx) are exquisitely sensitive to reactive oxygen stress. Furthermore, we have shown that npx is required for GBS survival in both THP-1 and placental macrophages. In an in vivo murine model of ascending GBS vaginal infection during pregnancy, npx is required for invading reproductive tissues and is critical for inducing disease progression, including PPROM and preterm birth. Reproductive tissue cytokine production was also significantly diminished in Δnpx mutant-infected animals compared to that in animals infected with wild-type (WT) GBS. Complementation in trans reversed this phenotype, indicating that npx is critical for GBS survival and the initiation of proinflammatory signaling in the gravid host. IMPORTANCE This study sheds new light on the way that group B Streptococcus (GBS) defends itself against oxidative stress in the infected host. The enzyme encoded by the GBS gene npx is an NADH peroxidase that, our study reveals, provides defense against macrophage-derived reactive oxygen stress and facilitates infections of the uterus during pregnancy. This enzyme could represent a tractable target for future treatment strategies against invasive GBS infections.


Asunto(s)
Corioamnionitis , Nacimiento Prematuro , Infecciones Estreptocócicas , Embarazo , Humanos , Femenino , Recién Nacido , Animales , Ratones , Placenta , Streptococcus agalactiae , Virulencia , Corioamnionitis/microbiología , Macrófagos , Infecciones Estreptocócicas/microbiología , Oxígeno
18.
Nat Commun ; 13(1): 5392, 2022 09 14.
Artículo en Inglés | MEDLINE | ID: mdl-36104331

RESUMEN

Perinatal infection with Streptococcus agalactiae, or Group B Streptococcus (GBS), is associated with preterm birth, neonatal sepsis, and stillbirth. Here, we study the interactions of GBS with macrophages, essential sentinel immune cells that defend the gravid reproductive tract. Transcriptional analyses of GBS-macrophage co-cultures reveal enhanced expression of a gene encoding a putative metal resistance determinant, cadD. Deletion of cadD reduces GBS survival in macrophages, metal efflux, and resistance to metal toxicity. In a mouse model of ascending infection during pregnancy, the ΔcadD strain displays attenuated bacterial burden, inflammation, and cytokine production in gestational tissues. Furthermore, depletion of host macrophages alters cytokine expression and decreases GBS invasion in a cadD-dependent fashion. Our results indicate that GBS cadD plays an important role in metal detoxification, which promotes immune evasion and bacterial proliferation in the pregnant host.


Asunto(s)
Nacimiento Prematuro , Streptococcus agalactiae , Animales , Citocinas , Femenino , Humanos , Recién Nacido , Recuento de Leucocitos , Macrófagos/microbiología , Metales , Ratones , Embarazo , Nacimiento Prematuro/microbiología , Streptococcus agalactiae/genética
19.
Metallomics ; 13(1)2021 01 16.
Artículo en Inglés | MEDLINE | ID: mdl-33570133

RESUMEN

Epsilonproteobacteria are a diverse class of eubacteria within the Proteobacteria phylum that includes environmental sulfur-reducing bacteria and the human pathogens, Campylobacter jejuni and Helicobacter pylori. These pathogens infect and proliferate within the gastrointestinal tracts of multiple animal hosts, including humans, and cause a variety of disease outcomes. While infection of these hosts provides nutrients for the pathogenic Epsilonproteobacteria, many hosts have evolved a variety of strategies to either sequester metals from the invading pathogen or exploit the toxicity of metals and drive their accumulation as an antimicrobial strategy. As a result, C. jejuni and H. pylori have developed mechanisms to sense changes in metal availability and regulate their physiology in order to respond to either metal limitation or accumulation. In this review, we will discuss the challenges of metal availability at the host-pathogen interface during infection with C. jejuni and H. pylori and describe what is currently known about how these organisms alter their gene expression and/or deploy bacterial virulence factors in response to these environments.


Asunto(s)
Campylobacter jejuni/metabolismo , Helicobacter pylori/metabolismo , Homeostasis , Metales Pesados/metabolismo , Transporte Biológico
20.
ACS Infect Dis ; 7(12): 3254-3263, 2021 12 10.
Artículo en Inglés | MEDLINE | ID: mdl-34812035

RESUMEN

Acinetobacter baumannii is a serious threat to human health, per the Centers for Disease Control and Prevention's latest threat assessment. A. baumannii is a Gram-negative opportunistic bacterial pathogen that causes severe community and nosocomial infections in immunocompromised patients. Treatment of these infections is confounded by the emergence of multi- and pan-drug resistant strains of A. baumannii. A. baumannii colonizes abiotic and biotic surfaces and evades antimicrobial challenges by forming biofilms, which are three-dimensional architectural structures of cells adhered to a substrate and encased in an extracellular matrix comprised of polymeric substances such as polysaccharides, proteins, and DNA. Biofilm-inhibiting compounds have recently gained attention as a chemotherapeutic strategy to prevent or disperse A. baumannii biofilms and restore the utility of traditional antimicrobial strategies. Recent work indicates that human milk oligosaccharides (HMOs) have potent antibacterial and biofilm-inhibiting properties. We sought to test the utility of HMOs against a bank of clinical isolates of A. baumannii to ascertain changes in bacterial growth or biofilm formation. Our results indicate that out of 18 strains tested, 14 were susceptible to the antibiofilm activities of HMOs, and that the potent antibiofilm activity was observed in strains isolated from diverse anatomical sites, disease manifestations, and across antibiotic-resistant and susceptible strains.


Asunto(s)
Acinetobacter baumannii , Antibacterianos/farmacología , Biopelículas , Humanos , Leche Humana , Oligosacáridos/farmacología
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