A New Class of Quorum Quenching Molecules from Staphylococcus Species Affects Communication and Growth of Gram-Negative Bacteria

The knowledge that many pathogens rely on cell-to-cell communication mechanisms known as quorum sensing, opens a new disease control strategy: quorum quenching. Here we report on one of the rare examples where Gram-positive bacteria, the ‘Staphylococcus intermedius group’ of zoonotic pathogens, excrete two compounds in millimolar concentrations that suppress the quorum sensing signaling and inhibit the growth of a broad spectrum of Gram-negative beta- and gamma-proteobacteria. These compounds were isolated from Staphylococcus delphini. They represent a new class of quorum quenchers with the chemical formula N-[2-(1H-indol-3-yl)ethyl]-urea and N-(2-phenethyl)-urea, which we named yayurea A and B, respectively. In vitro studies with the N-acyl homoserine lactone (AHL) responding receptor LuxN of V. harveyi indicated that both compounds caused opposite effects on phosphorylation to those caused by AHL. This explains the quorum quenching activity. Staphylococcal strains producing yayurea A and B clearly benefit from an increased competitiveness in a mixed community.     

High Prevalence of Cryptococcal Antigenemia among HIV-infected Patients Receiving Antiretroviral Therapy in Ethiopia

Background

Cryptococcal disease is estimated to be responsible for significant mortality in Sub-Saharan Africa; however, only scarce epidemiology data exists. We sought to evaluate the prevalence of and risk factors for cryptococcal antigenemia in Ethiopia.

Methods

Consecutive adult HIV-infected patients from two public HIV clinics in Addis Ababa, Ethiopia were enrolled into the study. A CD4 count ≤200 cells/μl was required for study participation. Patients receiving anti-retroviral therapy (ART) were not excluded. A cryptococcal antigen test was performed for all patients along with an interview, physical exam, and medical chart abstraction. Logistic regression analysis was used to assess risk factors for cryptococcal antigenemia.

Results

369 HIV-infected patients were enrolled; mean CD4 123 cells/μl and 74% receiving ART. The overall prevalence of cryptococcal antigenemia was 8.4%; 11% in patients with a CD4 count <100 cells/μl, 8.9% with CD4 100 to 150 cells/μl and 5.7% with CD4150-200 cell/μl. 84% of patients with cryptococcal antigenemia were receiving ART. In multivariable analysis, increasing age, self reported fever, CD4 count <100 cells/μl, and site of screening were associated with an increased risk of cryptococcal antigenemia. No individual or combination of clinical symptoms had optimal sensitivity or specificity for cryptococcal antigenemia.

Conclusion

Cryptococcal antigenemia is high in Ethiopia and rapid scale up of screening programs is needed. Screening should be implemented for HIV-infected patients with low CD4 counts regardless of symptoms or receipt of ART. Further study into the effect of location and environment on cryptococcal disease is warranted.     

Prevalence and Predictors of Asymptomatic Malaria Parasitemia among Pregnant Women in the Rural Surroundings of Arbaminch Town,South Ethiopia

Background

In Sub-Saharan African countries, including Ethiopia, malaria in pregnancy is a major public health threat which results in significant morbidities and mortalities among pregnant women and their fetuses. In malaria endemic areas, Plasmodium infections tend to remain asymptomatic yet causing significant problems like maternal anemia, low birth weight, premature births, and still birth. This study was conducted to determine the prevalence and predictors of asymptomatic Plasmodium infection among pregnant women in the rural surroundings of Arba Minch Town, Southern Ethiopia.

Methods

A community based cross-sectional study comprising multistage sampling was conducted between April and June, 2013. Socio-demographic data were collected by using a semi-structured questionnaire. Plasmodium infection was diagnosed by using Giemsa-stained blood smear microscopy and a rapid diagnostic test (SD BIOLINE Malaria Ag Pf/Pv POCT, standard diagnostics, inc., Korea).

Results

Of the total 341 pregnant women participated in this study, 9.1% (31/341) and 9.7% (33/341) were confirmed to be infected with Plasmodium species by microscopy and rapid diagnostic tests (RDTs), respectively. The geometric mean of parasite density was 2392 parasites per microliter (μl); 2275/ μl for P. falciparum and 2032/ μl for P. vivax. Parasitemia was more likely to occur in primigravidae (Adjusted odds ratio (AOR): 9.4, 95% confidence interval (CI): 4.3–60.5), secundigravidae (AOR: 6.3, 95% CI: 2.9–27.3), using insecticide treated bed net (ITN) sometimes (AOR: 3.2, 95% CI: 1.8- 57.9), not using ITN at all (AOR: 4.6, 95% CI: 1.4–14.4) compared to multigravidae and using ITN always, respectively.

Conclusion

Asymptomatic malaria in this study is low compared to other studies’ findings. Nevertheless, given the high risk of malaria during pregnancy, pregnant women essentially be screened for asymptomatic Plasmodium infection and be treated promptly via the antenatal care (ANC) services.     

Association and impact of <Emphasis Type="Italic">XPG Asp</Emphasis> 1104 <Emphasis Type="Italic">His</Emphasis> gene polymorphism in HIV 1 disease progression to AIDS among north Indian HIV seropositive individuals

Various efforts made to stop the deadly epidemic of HIV since its discovery in 1983 remain unsuccessful and this virus still continues to claim the lives of millions of individuals every year. The viral effect in the cell is complicated and the overall disease outcome is the result of interaction between a few viral proteins and complex host immune response. Because it has been reported that XPG (Xeroderma pigementesum group G) gene does play a role in reducing UV induced apoptosis and participate in Nucleotide Excision Repair (NER) process of DNA damage, it was hypothesized that polymorphism in this gene may have a role in HIV 1 disease progression to AIDS. The aim of the present study, therefore, was to find out the association between XPG gene polymorphism and its effect on the rate of HIV 1 disease progression to AIDS. 300 HIV seropositive cases and an equal number of age and sex matched controls were recruited for the study from north Indian population. The PCR-RFLP method was utilized to genotype 600 study subject for the XPG Asp ¹¹⁰⁴ His gene polymorphism. There was significant difference in the frequency of the His/His variant genotype (OR 1.95, 95% CI = 1.93–3.63, P = 0.04) between cases and controls indicating a probable role of this gene in host viral interactions.     

DNA repair genes polymorphism (<Emphasis Type="Italic">XPG</Emphasis> and <Emphasis Type="Italic">XRCC1</Emphasis>) and association of prostate cancer in a north Indian population

Prostate cancer is the most commonly diagnosed cancer in men worldwide and is the second leading cause of cancer related mortality. Genetic background may account for the difference in susceptibility of individuals to different diseases and the relationship between genetic polymorphism and some diseases has been extensively studied. There are several common polymorphisms in genes encoding DNA repair enzymes, some of these polymorphisms are reported to result in subtle structural alterations of the repair enzyme and modulation of the repair capacity. The aim of the present study was to analyze the effect of XPG Asp 1104His and XRCC1 Arg309Gln polymorphisms on risk of prostate cancer in north Indian population. Statistically significant increased risk of prostate cancer was observed on individuals that posses His/His genotype of XPG (OR 2.53, 95% CI 0.99–6.56, P = 0.031). In this study 150 prostate cancer diagnosed patients, 150 healthy controls and 150 BPH (benign prostate hyper plasia) were recruited from north Indian population. Moreover, individuals that carried the Gln/Gln genotype of XRCC1 also showed statistically increased risk of prostate cancer (OR 2.06, 95% CI 1.07–4.00, P = 0.033). The Asp/Asp of XPG and Gln/Gln of XRCC1 in combination showed statistically increased risk of prostate cancer in cases (OR 3.29, 95% CI 1.09–10.16, P = 0.032).     

Delay in diagnosis of pulmonary tuberculosis in low-and middle-income settings: systematic review and meta-analysis

Background

Assessment of delays in seeking care and diagnosis of tuberculosis is essential to evaluate effectiveness of tuberculosis control programs, and identify programmatic impediments. Thus, this review of studies aimed to examine the extent of patient, health system, and total delays in diagnosis of pulmonary tuberculosis in low- and middle- income countries.

Methods

It was done following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Electronic databases were searched to retrieve studies published from 2007 to 2015 including Pubmed central, Springer link, Hinari and Google scholar. Searching terms were pulmonary tuberculosis, health care seeking, health care seeking behavior, patient delay, diagnostic delay, health system delay, provider delay, and doctor delay. Retrieved studies were systematically reviewed and summarized using Comprehensive Meta-analysis software.

Results

Forty studies involving 18,975 patients qualified for systematic review, and 14 of them qualified for meta-analysis. The median diagnostic delay ranged from 30 to 366.5 days [IQR?=?44–77.8], with a 4–199 days [IQR?=?15–50] and 2–128.5 days [IQR?=?12–34] due to patient and health system delays, respectively. The meta-analysis showed 42% of pulmonary tuberculosis patients delayed seeking care by a month or more; uneducated patients [pooled OR?=?1.5, 95%CI?=?1.1–1.9] and those who sought initial care from informal providers [pooled OR?=?3, 95%CI?=?2.3–3.9] had higher odds of patient delay.

Conclusion

Delay in diagnosis is still a major challenge of tuberculosis control and prevention programs in low- and middle- income settings. Efforts to develop new strategies for better case-finding using the existing systems and improving patients’ care seeking behavior need to be intensified.

     

SadA-Expressing Staphylococci in the Human Gut Show Increased Cell Adherence and Internalization

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Traffic Noise and Inequality in the Twin Cities,Minnesota

It is widely known that prolonged exposure to high levels of traffic noise has several health effects. While scholarship in environmental justice has explored the environmental equity hypothesis in a wide range of areas, whether the spatial distribution of traffic noise is equitable among different racial and socioeconomic groups has rarely been explored, especially in the United States. This article addresses this lacuna by examining this relationship in the Twin Cities Metro Region, Minnesota. Traffic data from the Minnesota Department of Transportation were used to model the propagation of traffic noise over the study area and aircraft noise contour lines were added to account for aircraft noise. Inequities associated with exposure to chronic traffic noise were investigated using selected demographic and socioeconomic variables from the U.S. Census 2000. Statistical analysis was based on a regression model that addressed spatial autocorrelation. Results indicate that there is an association between noise levels and household income, median household value, the percentage of non-white residents, and the percentage of the population less than 18 years of age.     

Staphylococcal peptidoglycan co-localizes with Nod2 and TLR2 and activates innate immune response via both receptors in primary murine keratinocytes

In mammalian host cells staphylococcal peptidoglycan (PGN) is recognized by Nod2. Whether PGN is also recognized by TLR2 is disputed. Here we carried out PGN co-localization and stimulation studies with TLR2 and Nod2 in wild type and mutant host cells. To exclude contamination with lipoproteins, polymeric staphylococcal PGN (PGN(pol)) was isolated from Staphylococcus aureus Δlgt (lacking lipidated prelipoproteins). PGN(pol) was biotinylated (PGN-Bio) for fluorescence monitoring with specific antibodies. Keratinocytes from murine oral epithelium (MK) readily internalized PGN-Bio in an endocytosis-like process. In wt MK, PGN(pol) induced intracellular accumulation of Nod2 and TLR2 and co-localized with Nod2 and TLR2, but not with TLR4. In TLR2-deficient MK Nod2 and in Nod2-deficient MK TLR2 was induced, indicating that PGN(pol) recognition by Nod2 is independent of TLR2 and vice versa. In both mutants IL-6 and IL-1B release was decreased by approximately 50% compared to wt MK, suggesting that the immune responses induced by Nod2 and TLR2 are comparable and that the two receptors act additively in MK. In TLR2-transfected HEK293 cells PGN(pol) induced NFkB-promoter fused luciferase expression. To support the data, co-localization and signaling studies were carried out with SHL-PGN, a lipase protein covalently tethered to PGN-fragments of varying sizes at its C-terminus. SHL-PGN also co-localized with Nod2 or TLR2 and induced their accumulation, while SHL without PGN did not. The results show that staphylococcal PGN not only co-localizes with Nod2 but also with TLR2. PGN is able to stimulate the immune system via both receptors.