Amal Amer

By Estelle Cormet-Boyaka, Kyle Caution and Amal O. Amer

Cystic fibrosis (CF) is a fatal, genetic disorder that critically affects the lungs and is directly caused by mutations in the CF transmembrane conductance regulator (CFTR) gene, resulting in defective CFTR function. In epithelial cells, the CFTR channel conducts anions and plays a critical role in regulating the volume and composition of airway surface liquid. This thin layer of aqueous fluid and mucus covering the airway surface facilitates mucociliary clearance, bacterial killing, and epithelial cell homeostasis. The importance of the CFTR channel in macrophages was revealed in recent work that demonstrated that defective CFTR function is accompanied by impaired innate immune responses to specific infections. Notably, most CF-associated infections are caused by microbes that are cleared by autophagy in healthy cells. Autophagy is a highly regulated biological process that provides energy during periods of stress and starvation. Autophagy clears pathogens, inflammatory molecules, and dysfunctional protein aggregates within macrophages. However, this process is impaired in CF patients and CF mice, as their cells exhibit limited autophagy activity. The mechanisms linking a malfunctioning ion channel function to the defective autophagy remains unclear. In this chapter, we describe and discuss the recent findings indicating the presence of several mechanisms leading to defective autophagy in CF cells. Thus, these novel data advance our understanding of mechanisms underlying the pathobiology of CF and provide a new therapeutic platform for restoring CFTR function and autophagy in patients with CF.

Part of the book: Autophagy in Current Trends in Cellular Physiology and Pathology

By Arwa Abu Khweek and Amal O. Amer

Legionella pneumophila (L. pneumophila) is the causative agent of Legionnaires’ disease. Transmission to humans is mediated via inhalation of contaminated water droplets. L. pneumophila is widely distributed in man-made water systems, multiple species of protozoa, and nematodes. L. pneumophila persist within multi-species biofilms that cover surfaces within water systems. Virulence, spread, and resistance to biocides are associated with survival of L. pneumophila within multi-organismal biofilm. Outbreaks of Legionellosis are correlated with the existence of L. pneumophila in biofilms, even after the intensive chemical and physical treatments. Several factors negatively or positively modulate the persistence of L. pneumophila within the microbial consortium-containing L. pneumophila. Biofilm-forming L. pneumophila continue to be a public health and economic burden and directly influence the medical and industrial sectors. Diagnosis and hospitalization of patients and prevention protocols cost governments billions of dollars. Dissecting the biological and environmental factors that promote the persistence and physiological adaptation in biofilms can be fundamental to eliminating and preventing the transmission of L. pneumophila. Herein, we review different factors that promote persistence of L. pneumophila within the biofilm consortium, survival strategies used by the bacteria within biofilm community, gene regulation, and finally challenges associated with biofilm resistance to biocides and anti-Legionella treatments.

Part of the book: Bacterial Biofilms