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Magic bullets for the 21st century: the reemergence of immunotherapy for multi- and pan-resistant microbes.

ABSTRACT: In our current world, antibiotic resistance among pathogenic microbes keeps getting worse with few new antibiotics being pursued by pharmaceutical companies. Modern-day immunotherapies, reminiscent of the serotherapy approaches used in the early days of antimicrobial treatments, are a potential counter-measure, but are usually limited by the narrow spectrum against target antigens. Surprisingly, many multidrug-resistant (MDR) bacteria share a common surface polysaccharide, poly-?-1,6-N-acetylglucosamine (PNAG). Natural antibodies to PNAG are present in normal human sera, but are not protective. However, human monoclonal antibodies (MAbs) or polyclonal antisera raised to a deacetylated glycoform of PNAG mediate opsonic killing and protect mice against infections due to all PNAG-positive MDR pathogens tested. An MAb is currently in Phase II clinical trials. These discoveries could lead to utilization of antibodies to PNAG for either therapeutic use in patients infected by PNAG-producing MDR bacteria or prophylactic use in patients at risk of developing MDR infections.

SUBMITTER: Roux D

PROVIDER: S-EPMC3695597 | biostudies-literature | 2012 Dec

REPOSITORIES: biostudies-literature

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Magic bullets for the 21st century: the reemergence of immunotherapy for multi- and pan-resistant microbes.

Roux Damien D Pier Gerald B GB Skurnik David D

The Journal of antimicrobial chemotherapy 20120816 12

In our current world, antibiotic resistance among pathogenic microbes keeps getting worse with few new antibiotics being pursued by pharmaceutical companies. Modern-day immunotherapies, reminiscent of the serotherapy approaches used in the early days of antimicrobial treatments, are a potential counter-measure, but are usually limited by the narrow spectrum against target antigens. Surprisingly, many multidrug-resistant (MDR) bacteria share a common surface polysaccharide, poly-β-1,6-N-acetylglu ...[more]

PMID: 22899807

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Project description:There is no good science in bad models. Cell culture is especially prone to artifacts. A number of novel cell culture technologies have become more broadly available in the 21st century, which allow overcoming limitations of traditional culture and are more physiologically relevant. These include the use of stem-cell derived human cells, cocultures of different cell types, scaffolds and extracellular matrices, perfusion platforms (such as microfluidics), 3D culture, organ-on-chip technologies, tissue architecture, and organ functionality. The physiological relevance of such models is further enhanced by the measurement of biomarkers (e.g., key events of pathways), organ specific functionality, and more comprehensive assessment cell responses by high-content methods. These approaches are still rarely combined to create microphysiological systems. The complexity of the combination of these technologies can generate results closer to the in vivo situation but increases the number of parameters to control, bringing some new challenges. In fact, we do not argue that all cell culture needs to be that sophisticated. The efforts taken are determined by the purpose of our experiments and tests. If only a very specific molecular target to cell response is of interest, a very simple model, which reflects this, might be much more suited to allow standardization and high-throughput. However, the less defined the end point of interest and cellular response are, the better we should approximate organ- or tissue-like culture conditions to make physiological responses more probable. Besides these technologic advances, important progress in the quality assurance and reporting on cell cultures as well as the validation of cellular test systems brings the utility of cell cultures to a new level. The advancement and broader implementation of Good Cell Culture Practice (GCCP) is key here. In toxicology, this is a major prerequisite for meaningful and reliable results, ultimately supporting risk assessment and product development decisions.

Dataset Information

Magic bullets for the 21st century: the reemergence of immunotherapy for multi- and pan-resistant microbes.

Publications

Magic bullets for the 21st century: the reemergence of immunotherapy for multi- and pan-resistant microbes.

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