Recent advances in the therapeutic potential of cathelicidins.

The alarming increase in antimicrobial resistance in the last decades has prompted the search for alternatives to control infectious diseases. Antimicrobial peptides (AMPs) represent a heterogeneous class of molecules with ample antibacterial, antiviral, and antifungal effects. They can be found in many organisms, including all classes of vertebrates, providing a valuable source of new antimicrobial agents. The unique properties of AMPs make it harder for microbes develop resistance, while their immunomodulatory properties and target diversity reinforce their translational use in multiple diseases, from autoimmune disorders to different types of cancer. The latest years have witnessed a vast number of studies evaluating the use of AMPs in therapy, with many progressing to clinical trials. The present review explores the recent developments in the medicinal properties of cathelicidins, a vast family of AMPs with potent antimicrobial and immunomodulatory effects. Cathelicidins from several organisms have been tested in disease models of viral and bacterial infections, inflammatory diseases, and tumors, with encouraging results. Combining nanomaterials with active, natural antimicrobial peptides, including LL-37 and synthetic analogs like ceragenins, leads to the creation of innovative nanoagents with significant clinical promise. However, there are still important limitations, such as the toxicity of many cathelicidins to healthy host cells and low stability in vivo. The recent advances in nanomaterials and synthetic biology may help overcome the current limitations, enabling the use of cathelicidins in future therapeutics. Furthermore, a better understanding of the mechanisms of cathelicidin action in vivo and their synergy with other host molecules will contribute to the development of safer, highly effective therapies.

Klebsiella pneumoniae Biofilms and Their Role in Disease Pathogenesis.

The ability to form biofilms is a crucial virulence trait for several microorganisms, including Klebsiella pneumoniae - a Gram-negative encapsulated bacterium often associated with nosocomial infections. It is estimated that 65-80% of bacterial infections are biofilm related. Biofilms are complex bacterial communities composed of one or more species encased in an extracellular matrix made of proteins, carbohydrates and genetic material derived from the bacteria themselves as well as from the host. Bacteria in the biofilm are shielded from immune responses and antibiotics. The present review discusses the characteristics of K. pneumoniae biofilms, factors affecting biofilm development, and their contribution to infections. We also explore different model systems designed to study biofilm formation in this species. A great number of factors contribute to biofilm establishment and maintenance in K. pneumoniae, which highlights the importance of this mechanism for the bacterial fitness. Some of these molecules could be used in future vaccines against this bacterium. However, there is still a lack of in vivo models to evaluate the contribution of biofilm development to disease pathogenesis. With that in mind, the combination of different methodologies has great potential to provide a more detailed scenario that more accurately reflects the steps and progression of natural infection.