This study aims to provide an updated survey of the main synthesis methods of copper oxide (CuO) nanoparticles in order to obtain tailored nanosystems for various biomedical applications. The synthesis approach significantly impacts the properties of such nanoparticles and these properties in turn have a significant impact on their biomedical applications. Although not widely investigated as an efficient drug delivery system, CuO nanoparticles have great biological properties including effective antimicrobial action against a wide range of pathogens and also drug resistant bacteria. These properties have led to the development of various approaches with direct applications to the biomedical field, such as tailored surfaces with antimicrobial effect, wound dressings and modified textiles. It is also believed that these nanosystems could represent efficient alternatives in the development of smart systems utilized both for the detection of pathogens and for the treatment of infections.

Abstract:The use of nanoparticles has contributed to many advances due to their important properties such as, size, shape or biocompatibility. The use of nanotechnology in medicine has great potential, especially in medical microbiology. Promising data show the possibility of shaping immune responses and fighting severe infections using synthetic materials. Different studies have suggested that the addition of synthetic nanoparticles in vaccines and immunotherapy will have a great impact on public health. On the other hand, antibiotic resistance is one of the major concerns worldwide; a recent report of the World Health Organization (WHO) states that antibiotic resistance could cause 300 million deaths by 2050. Nanomedicine offers an innovative tool for combating the high rates of resistance that we are fighting nowadays, by the development of both alternative therapeutic and prophylaxis approaches and also novel diagnosis methods. Early detection of infectious diseases is the key to a successful treatment and the new developed applications based on nanotechnology offer an increased sensibility and efficiency of the diagnosis. The aim of this review is to reveal and discuss the main advances made on the science of nanomaterials for the prevention, diagnosis and treatment of infectious diseases. Highlighting innovative approaches utilized to: (i) increasing the efficiency of vaccines; (ii) obtaining shuttle systems that require lower antibiotic concentrations; (iii) developing coating devices that inhibit microbial colonization and biofilm formation.

Well-adapted pathogens must evade clearance by the host immune system and the study of how they do this has revealed myriad complex strategies and mechanisms. Classical bordetellae are very closely related subspecies that are known to modulate adaptive immunity in a variety of ways, permitting them to either persist for life or repeatedly infect the same host. Exploring the hypothesis that exposure to immune cells would cause bordetellae to induce expression of important immunomodulatory mechanisms, we identified a putative regulator of an immunomodulatory pathway. The deletion of btrS in B. bronchiseptica did not affect colonization or initial growth in the respiratory tract of mice, its natural host, but did increase activation of the inflammasome pathway, and recruitment of inflammatory cells. The mutant lacking btrS recruited many more B and T cells into the lungs, where they rapidly formed highly organized and distinctive Bronchial Associated Lymphoid Tissue (BALT) not induced by any wild type Bordetella species, and a much more rapid and strong antibody response than observed with any of these species. Immunity induced by the mutant was measurably more robust in all respiratory organs, providing completely sterilizing immunity that protected against challenge infections for many months. Moreover, the mutant induced sterilizing immunity against infection with other classical bordetellae, including B. pertussis and B. parapertussis, something the current vaccines do not provide. These findings reveal profound immunomodulation by bordetellae and demonstrate that by disrupting it much more robust protective immunity can be generated, providing a pathway to greatly improve vaccines and preventive treatments against these important pathogens.

Wound healing involves a complex interaction between immunity and other natural host processes, and to succeed it requires a well-defined cascade of events. Chronic wound infections can be mono- or polymicrobial but their major characteristic is their ability to develop a biofilm. A biofilm reduces the effectiveness of treatment and increases resistance. A biofilm is an ecosystem on its own, enabling the bacteria and the host to establish different social interactions, such as competition or cooperation. With an increasing incidence of chronic wounds and, implicitly, of chronic biofilm infections, there is a need for alternative therapeutic agents. Nanotechnology shows promising openings, either by the intrinsic antimicrobial properties of nanoparticles or their function as drug carriers. Nanoparticles and nanostructured coatings can be active at low concentrations toward a large variety of infectious agents; thus, they are unlikely to elicit emergence of resistance. Nanoparticles might contribute to the modulation of microbial colonization and biofilm formation in wounds. This comprehensive review comprises the pathogenesis of chronic wounds, the role of chronic wound colonization and infection in the healing process, the conventional and alternative topical therapeutic approaches designed to combat infection and stimulate healing, as well as revolutionizing therapies such as nanotechnology-based wound healing approaches.

The classical bordetellae sense and respond to a variety of environments outside and within their mammalian hosts. By causing inflammation and tissue damage, we reasoned that bordetellae are likely to encounter components of blood and/or serum during the course of a respiratory infection, and that detecting and responding to these would be advantageous. Therefore, we hypothesized that classical bordetellae have the ability to sense and respond to blood or serum. Blood or serum exposure resulted in substantial transcriptional changes in Bordetella bronchiseptica, including enhanced expression of many virulence-associated genes. Exposure to blood or serum additionally elicited production of multiple antigens not otherwise detectable, and led to increased bacterial cytotoxicity against macrophages. Transcriptional responses to blood/serum were observed in a Bvg− phase-locked mutant, indicating that the response is not solely dependent on a functional BvgAS system. Similar transcriptional responses to blood/serum were observed for the other classical bordetellae, Bordetella pertussis and Bordetella parapertussis. These data suggest the classical bordetellae respond to signals present in blood and serum by changing their behavior in ways that likely contribute to their remarkable success, via effects on pathogenesis, persistence and/or transmission between hosts.

The mammalian immune system includes a sophisticated array of antimicrobial mechanisms. However, successful pathogens have developed subversive strategies to detect, modulate, and/or evade immune control and clearance. Independent disciplines study host immunology and bacterial pathogenesis, but interkingdom signaling between bacteria and host during natural infection remains poorly understood. An efficient natural host infection system has revealed complex communication between Bordetella spp. and mice, identified novel regulatory mechanisms and demonstrated that bordetellae can respond to microenvironment and inflammatory status cues. Understanding these bacterial signaling pathways and the complex network of them that allows precisely timed expression of numerous immunomodulatory factors will serve as a paradigm for other organisms lacking such a powerful experimental infection system.

This paper reports the synthesis and characterization of amoxicillinfunctionalized magnetite nanostructures (Fe 3 O 4 @AMO), revealing and discussing several biomedical applications of these nanomaterials. Our results proved that 10 nm Fe 3 O 4 @AMO nanoparticles does not alter the normal cell cycle progression of cultured OPEN ACCESSMolecules 2014, 19 5014 diploid cells, and an in vivo murine model confirms that the nanostructures disperse through the host body and tend to localize in particular sites and organs. The nanoparticles were found clustered especially in the lungs, kidneys and spleen, next to the blood vessels at this level, while being totally absent in the brain and liver, suggesting that they are circulated through the blood flow and have low toxicity. Fe 3 O 4 @AMO has the ability to be easily circulated through the body and optimizations may be done so these nanostructures cluster to a specific target region. Functionalized magnetite nanostructures proved a great antimicrobial effect, being active against both the Gram positive pathogen S. aureus and the Gram negative pathogen E. coli. The fabricated nanostructures significantly reduced the minimum inhibitory concentration (MIC) of the active drug. This result has a great practical relevance, since the functionalized nanostructures may be used for decreasing the therapeutic doses which usually manifest great severe side effects, when administrated in high doses. Fe 3 O 4 @AMO represents also a suitable approach for the development of new alternative strategies for improving the activity of therapeutic agents by targeted delivery and controlled release.

Recent findings revealed pivotal roles for eosinophils in protection against parasitic and viral infections, as well as modulation of adaptive immune responses in the gastric mucosa. However, the known effects of eosinophils within the respiratory tract remain predominantly pathological, associated with allergy and asthma. Simulating natural respiratory infections in mice, we examined how efficient and well-adapted pathogens can block eosinophil functions that contribute to the immune response. Bordetella bronchiseptica, a natural pathogen of the mouse, uses the sigma factor btrS to regulate expression of mechanisms that interfere with eosinophil recruitment and function. When btrS is disrupted, immunomodulators are dysregulated, and eosinophils are recruited to the lungs, suggesting they may contribute to much more efficient generation of adaptive immunity induced by this mutant. Eosinophil-deficient mice failed to produce pro-inflammatory cytokines, to recruit lymphocytes, to organize lymphoid aggregates that resemble Bronchus Associated Lymphoid Tissue (BALT), to generate an effective antibody response, and to clear bacterial infection from the respiratory tract. Importantly, the failure of eosinophil-deficient mice to produce these lymphoid aggregates indicates that eosinophils can mediate the generation of an effective lymphoid response in the lungs. These data demonstrate that efficient respiratory pathogens can block eosinophil recruitment, to inhibit the generation of robust adaptive immune responses. They also suggest that some post-infection sequelae involving eosinophils, such as allergy and asthma, might be a consequence of bacterial mechanisms that manipulate their accumulation and/or function within the respiratory tract.