Streptococcus pneumoniae Carriage in the Gaza Strip

Background: Pneumococcal infections cause major morbidity and mortality in developing countries. We report the epidemiology of S. pneumoniae carriage in a developing region, the Gaza strip, and evaluate the theoretical coverage of carriage strains by pneumococcal conjugate vaccines (PCVs). Methodology: In 2009 we conducted a cross-sectional survey of S. pneumoniae carriage in healthy children and their parents, living throughout the Gaza strip. Data were collected and nasopharyngeal swabs were obtained. Antibiotic susceptibilities were determined by Vitek-2 and serotypes by the Quellung reaction. Principal Findings: S. pneumoniae carriage was detected in 189/379 (50%) of children and 30/376 (8%) of parents. Carriage prevalence was highest in children <6 months of age (63%). Significant predictors for child carriage were number of household members and DCC attendance. The proportion of pediatric and adults isolates with serotypes included in PCV7 were 32% and 20% respectively, and 46% and 33% in PCV13 respectively. The most prominent non-vaccine serotypes (NVT) were 35B, 15B/C and 23B. Penicillin-nonsusceptible strains were carried by 70% of carriers, penicillin-resistant strains (PRSP) by 13% and Multi-drug-resistant (MDR) by 30%. Of all PRSP isolates 54% belonged to serotypes included in PCV7 and 71% in the PCV13. Similarly, 59% and 73% of MDR-SP isolates, would theoretically be covered by PCV7 and PCV13, respectively. Conclusions: This study demonstrates that, PCV13-included strains were carried by 46% and 33% of pediatric and adult subjects respectively. In the absence of definitive data regarding the virulence of the NVT strains, it is difficult to predict the effect of PCVs on IPD in this region

Neutralising capacity against Delta and other variants of concern following Comirnaty vaccination in health care workers, Israel

Since its emergence, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has been responsible for more than 170 million cases and 3.5 million deaths. During December 2020 the Comirnaty (BNT162b2 mRNA, BioNTech-Pfizer, Mainz, Germany/New York, United States (US)) vaccine was approved by the US Food and Drug Administration and shown to be 95% efficacious in preventing symptomatic coronavirus disease 2019 (COVID-19). Clinical and real-world data demonstrated 95% effectiveness of the mRNA- based vaccine against the original SARS-CoV-2 and the Alpha variant. Since December 2020, several SARS-CoV-2 variants have emerged and were classified by the World Health Organization (WHO) as variants of concern (VOC): Alpha (Phylogenetic Assignment of Named Global Outbreak (Pango) lineage designation B.1.1.7), first detected in the United Kingdom (UK), Beta (B.1.351) first documented in South Africa [5] and Gamma (P.1) initially detected in Brazil. Most recently, in April 2021, the Delta (B.1.617.2) variant was identified in India and classified on May 11 as VOC due to its fast spread and potential immune escape. Here, we describe the neutralising response of sera from healthcare workers without prior SARS-CoV-2 infection following a second vaccine dose against viral isolates of the Delta VOC, and compared it to the response against isolates of the original, the Alpha, Beta and Gamma VOCs

Killing niche competitors by remote-control bacteriophage induction

A surprising example of interspecies competition is the production by certain bacteria of hydrogen peroxide at concentrations that are lethal for others. A case in point is the displacement of Staphylococcus aureus by Streptococcus pneumoniae in the nasopharynx, which is of considerable clinical significance. How it is accomplished, however, has been a great mystery, because H2O2 is a very well known disinfectant whose lethality is largely due to the production of hyperoxides through the abiological Fenton reaction. In this report, we have solved the mystery by showing that H2O2 at the concentrations typically produced by pneumococci kills lysogenic but not nonlysogenic staphylococci by inducing the SOS response. The SOS response, a stress response to DNA damage, not only invokes DNA repair mechanisms but also induces resident prophages, and the resulting lysis is responsible for H2O2 lethality. Because the vast majority of S. aureus strains are lysogenic, the production of H2O2 is a very widely effective antistaphylococcal strategy. Pneumococci, however, which are also commonly lysogenic and undergo SOS induction in response to DNA-damaging agents such as mitomycin C, are not SOS-induced on exposure to H2O2. This is apparently because they are resistant to the DNAdamaging effects of the Fenton reaction. The production of an SOS-inducing signal to activate prophages in neighboring organisms is thus a rather unique competitive strategy, which we suggest may be in widespread use for bacterial interference. However, this strategy has as a by-product the release of active phage, which can potentially spread mobile genetic elements carrying virulence genes.This work was supported by Comisión Interministerial de Ciencia y Tecnología Grants BIO2005-08399-C02-02, BIO2008-05284-C02-02, and BIO2008-00642-E/C; Cardenal Herrera-CEU University Grants PRCEUUCH25/ 08 and Copernicus program; and by Conselleria de Agricultura, Pesca i Alimentació (CAPiA), and from the Generalitat Valenciana (ACOMP07/258) (J.R.P.). L.S. and D.V. were supported by Cardenal Herrera-CEU University fellowships

Methicillin-resistant Staphylococcus aureus in Neonatal Intensive Care Unit

A neonatal intensive care unit outbreak was caused by a strain of methicillin-resistant Staphylococcus aureus previously found in the community (ST45-MRSA-IV). Fifteen infected neonates were identified, 2 of whom died. This outbreak illustrates how a rare community pathogen can rapidly spread through nosocomial transmission

Is methicillin-resistant Staphylococcus aureus replacing methicillin-susceptible S. aureus?

Despite extensive research on the emergence of and treatments for methicillin-resistant Staphylococcus aureus (MRSA), prior studies have not rigorously evaluated the impact of methicillin resistance on the overall incidence of S. aureus infections. Yet, there are direct clinical and research implications of determining whether methicillin-susceptible S. aureus (MSSA) infection rates remain stable in the face of increasing MRSA prevalence or whether MSSA will be replaced over time. A synthesis of prior studies indicates that the emergence of healthcare-associated MRSA (HA-MRSA) and community-associated MRSA (CA-MRSA) has led to an increase in the overall incidence of S. aureus infections, with MRSA principally adding to, rather than replacing, MSSA. However, colonization with CA-MRSA may at least partially replace colonization with MSSA. So far, evidence indicates that MSSA still accounts for many infections. Therefore, eradication of MRSA alone is not sufficient to address the public health burden of S. aureus

Interference between Streptococcus pneumoniae and Staphylococcus aureus: In Vitro Hydrogen Peroxide-Mediated Killing by Streptococcus pneumoniae

The bactericidal activity of Streptococcus pneumoniae toward Staphylococcus aureus is mediated by hydrogen peroxide. Catalase eliminated this activity. Pneumococci grown anaerobically or genetically lacking pyruvate oxidase (SpxB) were not bactericidal, nor were nonpneumococcal streptococci. These results provide a possible mechanistic explanation for the interspecies interference observed in epidemiologic studies

Antibiotics in agriculture and the risk to human health: how worried should we be?

The use of antibiotics in agriculture is routinely described as a major contributor to the clinical problem of resistant disease in human medicine. While a link is plausible, there are no data conclusively showing the magnitude of the threat emerging from agriculture. Here, we define the potential mechanisms by which agricultural antibiotic use could lead to human disease and use case studies to critically assess the potential risk from each. The three mechanisms considered are as follows 1: direct infection with resistant bacteria from an animal source, 2: breaches in the species barrier followed by sustained transmission in humans of resistant strains arising in livestock, and 3: transfer of resistance genes from agriculture into human pathogens. Of these, mechanism 1 is the most readily estimated, while significant is small in comparison with the overall burden of resistant disease. Several cases of mechanism 2 are known, and we discuss the likely livestock origins of resistant clones of Staphylococcus aureus and Enterococcus faecium, but while it is easy to show relatedness the direction of transmission is hard to assess in robust fashion. More difficult yet to study is the contribution of mechanism 3, which may be the most important of all

SpxB Is a Suicide Gene of Streptococcus pneumoniae and Confers a Selective Advantage in an In Vivo Competitive Colonization Model

The human bacterial pathogen Streptococcus pneumoniae dies spontaneously upon reaching stationary phase. The extent of S. pneumoniae death at stationary phase is unusual in bacteria and has been conventionally attributed to autolysis by the LytA amidase. In this study, we show that spontaneous pneumococcal death is due to hydrogen peroxide (H(2)O(2)), not LytA, and that the gene responsible for H(2)O(2) production (spxB) also confers a survival advantage in colonization. Survival of S. pneumoniae in stationary phase was significantly prolonged by eliminating H(2)O(2) in any of three ways: chemically by supplementing the media with catalase, metabolically by growing the bacteria under anaerobic conditions, or genetically by constructing DeltaspxB mutants that do not produce H(2)O(2). Likewise, addition of H(2)O(2) to exponentially growing S. pneumoniae resulted in a death rate similar to that of cells in stationary phase. While DeltalytA mutants did not lyse at stationary phase, they died at a rate similar to that of the wild-type strain. Furthermore, we show that the death process induced by H(2)O(2) has features of apoptosis, as evidenced by increased annexin V staining, decreased DNA content, and appearance as assessed by transmission electron microscopy. Finally, in an in vivo rat model of competitive colonization, the presence of spxB conferred a selective advantage over the DeltaspxB mutant, suggesting an explanation for the persistence of this gene. We conclude that a suicide gene of pneumococcus is spxB, which induces an apoptosis-like death in pneumococci and confers a selective advantage in nasopharyngeal cocolonization