Abstract
ABSTRACTThis review provides an overview of the most important novel treatment strategies against Streptococcus pneumoniae infections published over the past 10 years. The pneumococcus causes the majority of community-acquired bacterial pneumonia cases, and it is one of the prime pathogens in bacterial meningitis. Over the last 10 years, extensive research has been conducted to prevent severe pneumococcal infections, with a major focus on (i) boosting the host immune system and (ii) discovering novel antibacterials. Boosting the immune system can be done in two ways, either by actively modulating host immunity, mostly through administration of selective antibodies, or by interfering with pneumococcal virulence factors, thereby supporting the host immune system to effectively overcome an infection. While several of such experimental therapies are promising, few have evolved to clinical trials. The discovery of novel antibacterials is hampered by the high research and development costs versus the relatively low revenues for the pharmaceutical industry. Nevertheless, novel enzymatic assays and target-based drug design, allow the identification of targets and the development of novel molecules to effectively treat this life-threatening pathogen.
Highlights
Streptococcus pneumoniae, called the pneumococcus, is a major human pathogen
This review provides an overview of the most important novel treatment strategies against Streptococcus pneumoniae infections published over the past 10 years
Boosting the immune system can be done in two ways, either by actively modulating host immunity, mostly through administration of selective antibodies, or by interfering with pneumococcal virulence factors, thereby supporting the host immune system to effectively overcome an infection
Summary
1. Analogues of already marketed antibiotics are in development to overcome increasing pneumococcal resistance. Analogues of already marketed antibiotics are in development to overcome increasing pneumococcal resistance Several of these are currently undergoing clinical trials. 2. Antibacterial targets, consisting of pneumococcal enzymes essential for viability and survival, are being identified. Target-specific rational drug design, including highthroughput screening (HTS) against a major enzyme followed by elucidation of the structure-activity relationship (SAR) and subsequent lead optimization, shows promise in creating novel antibacterials. Alternative strategies including modulating the host immune system or inhibiting pneumococcal virulence are gaining scientific attention. None of these therapies have currently evolved to clinical trials
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