How to Combat Gram-Negative Bacteria Using Antimicrobial Peptides: A Challenge or an Unattainable Goal?

Antimicrobial peptides (AMPs) represent a promising and effective alternative for combating pathogens, having some advantages compared to conventional antibiotics. However, AMPs must also contend with complex and specialised Gram-negative bacteria envelops. The variety of lipopolysaccharide and phospholipid composition in Gram-negative bacteria strains and species are decisive characteristics regarding their susceptibility or resistance to AMPs. Such biological and structural barriers have created delays in tuning AMPs to deal with Gram-negative bacteria. This becomes even more acute because little is known about the interaction AMP–Gram-negative bacteria and/or AMPs’ physicochemical characteristics, which could lead to obtaining selective molecules against Gram-negative bacteria. As a consequence, available AMPs usually have highly associated haemolytic and/or cytotoxic activity. Only one AMP has so far been FDA approved and another two are currently in clinical trials against Gram-negative bacteria. Such a pessimistic panorama suggests that efforts should be concentrated on the search for new molecules, designs and strategies for combating infection caused by this type of microorganism. This review has therefore been aimed at describing the currently available AMPs for combating Gram-negative bacteria, exploring the characteristics of these bacteria’s cell envelop hampering the development of new AMPs, and offers a perspective regarding the challenges for designing new AMPs against Gram-negative bacteria.

Intersex Plays a Role in Microbial Homeostasis in the Brown Planthopper

Insects harbor a wide variety of symbiotic microorganisms that are capable of regulating host health and promoting host adaptation to their environment and food sources. However, there is little knowledge concerning the mechanisms that maintain the microbial community homeostasis within insects. In this study, we found that the intersex (ix) gene played an essential role in maintaining microbial homeostasis in the brown planthopper (BPH), Nilaparvata lugens. Injection of the double-strand RNA targeting N. lugens ix (Nlix) into the newly emerged females resulted in abnormal expansion of the copulatory bursa of BPH after mating. Further observation by transmission electron microscopy (TEM) revealed that the abnormally enlarged copulatory bursa resulting from dsNlix treatment was full of microorganisms, while in contrast, the copulatory bursa of dsGFP-treated individuals stored a large number of sperm accompanied by a few bacteria. Moreover, RNA-seq analysis showed that the gene responses to bacteria were remarkably enriched in differentially expressed genes (DEGs). In addition, 16s rRNA sequencing indicated that, compared with control samples, changes in the composition of microbes presented in dsNlix-treated copulatory bursa. Together, our results revealed the immune functions of the Nlix gene in maintaining microbial homeostasis and combating infection in BPH.

Experience in treatment of thermal burns in dogs

Burns take 3rd place among peacetime injuries and represent a major medical and veterinary problem [1]. Effective treatment of thermal burns in animals as well as prevention of post-burn complications are an important task for a veterinarian [2]. However the treatment of animal burns in veterinary medicine has not been sufficiently developed [3]. When prescribing treatment it is necessary to take into account the degree of burn, the area and depth of damage, the presence of complications, the general condition of the animal. It is important to know that with thermal burns not only local pathological and morphological changes occur, but also general changes on the part of various organs and systems in particular protein and water-salt metabolism is disrupted, toxins accumulate, the body's defenses are decreased, and burn exhaustion is developed. In this case the degree of the general reaction of the body directly depends on the depth and area of burns [4]. Therefore the treatment should provide for anesthesia, be aimed at combating infection and intoxication of the body, and also take into account the phases of the wound process and the peculiarities of their healing [5]. For the treatment of thermal burns in animals we have proposed two methods depending on the degree of burns: a bandage method for treating second-degree burns using a complex drug mixture No. 1 and a non-bandage method for treating third-degree burns using a complex drug mixture No. 2 in combination with a short novocaine blockade. Both have shown high therapeutic efficacy.

S100A8/A9 modulates inflammatory collateral tissue damage during intraperitoneal origin systemic candidiasis

Peritonitis is a leading cause of severe sepsis in surgical intensive care units, as over 70% of patients diagnosed with peritonitis develop septic shock. A critical role of the immune system is to return to homeostasis after combating infection. S100A8/A9 (calprotectin) is an antimicrobial, pro-inflammatory protein complex often used as a biomarker for diagnosis of disease activities in many inflammatory disorders. Here we describe the role of S100A8/A9 on inflammatory collateral tissue damage (ICTD).We performed an in vivo Candida albicans disseminated peritonitis mouse model using WT and S100A9-deficient mice and stimulated primary macrophages with recombinant S100A8/A9 in the presence or absence of the compound paquinimod, a specific inhibitor of S100A9. In addition, the effects on ICTD and fungal clearance were investigated. S100A9-deficient mice developed less ICTD than wildtype mice. Restoration of S100A8/A9 in S100A9 knockout mice resulted in increased ICTD and fungal clearance comparable to wildtype levels. Treatment with paquinimod abolished ICTD.The data indicated that S100A8/A9 controls ICTD levels and host antimicrobial modulation at a systemic level during intra-abdominal candidiasis (IAC).

Host–pathogen interactions and subversion of autophagy

Macroautophagy (‘autophagy’), is the process by which cells can form a double-membraned vesicle that encapsulates material to be degraded by the lysosome. This can include complex structures such as damaged mitochondria, peroxisomes, protein aggregates and large swathes of cytoplasm that can not be processed efficiently by other means of degradation. Recycling of amino acids and lipids through autophagy allows the cell to form intracellular pools that aid survival during periods of stress, including growth factor deprivation, amino acid starvation or a depleted oxygen supply. One of the major functions of autophagy that has emerged over the last decade is its importance as a safeguard against infection. The ability of autophagy to selectively target intracellular pathogens for destruction is now regarded as a key aspect of the innate immune response. However, pathogens have evolved mechanisms to either evade or reconfigure the autophagy pathway for their own survival. Understanding how pathogens interact with and manipulate the host autophagy pathway will hopefully provide a basis for combating infection and increase our understanding of the role and regulation of autophagy. Herein, we will discuss how the host cell can identify and target invading pathogens and how pathogens have adapted in order to evade destruction by the host cell. In particular, we will focus on interactions between the mammalian autophagy gene 8 (ATG8) proteins and the host and pathogen effector proteins.

ENTERAL/ORAL GLUTAMINE SUPPLEMENTATION IN PATIENTS FOLLOWING SURGERY AND ACCIDENTAL INJURY

ABSTRACTObjective: The objective of this investigation was to study the effect of enteral/oral glutamine supplementation in patients following abdominalsurgery on plasma glutamine levels, rate of infection, and length of hospitalization (LOH).Methods: A randomized control trial was used, and the patients were randomly divided into two groups, namely experimental and control with30 participants each. Glutamine supplement (0.5 g/kg) was administered (oral and enteral) to the experimental group for 5 days post-surgeryimmediately after the feeding began. The study was conducted in ESIC hospital, Chennai, India.Results: The incidence of infection in the control group was found to be almost twice that in the experimental group considering the role of glutaminein combating infection. Furthermore, the LOH was found to be slightly higher in the control group as compared to the experimental group.Conclusion: This study has provided evidence that the supplementation of enteral glutamine in post-operative patients decreases the incidence ofpost-surgical infection, shortening of hospital stay and reduction in the overall hospital costs.Keywords: Glutamine supplementation, Post-operative patients, Oral and enteral feed.

Modelling the lymphatic system: challenges and opportunities

The lymphatic system is a vital part of the circulatory and immune systems, and plays an important role in homeostasis by controlling extracellular fluid volume and in combating infection. Nevertheless, there is a notable disparity in terms of research effort expended in relation to the treatment of lymphatic diseases in contrast to the cardiovascular system. While similarities to the cardiovascular system exist, there are considerable differences in their anatomy and physiology. This review outlines some of the challenges and opportunities for those engaged in modelling biological systems. The study of the lymphatic system is still in its infancy, the vast majority of the models presented in the literature to date having been developed since 2003. The number of distinct models and their variants are few in number, and only one effort has been made thus far to study the entire lymphatic network; elements of the lymphatic system such as the nodes, which act as pumps and reservoirs, have not been addressed by mathematical models. Clearly, more work will be necessary in combination with experimental verification in order to progress and update the knowledge on the function of the lymphatic system. As our knowledge and understanding of its function increase, new and more effective treatments of lymphatic diseases are bound to emerge.