Intracellular survival protects bacterial pathogens from many antibiotics that need to cross host cellular membranes through diffusion or endocytosis to reach their targets. Because of this, more than two-thirds of the currently available antimicrobial treatments are ineffective against intracellular pathogens. In addition, intracellular pathogens reside in the cytosol or within different intracellular compartments. Therefore, antimicrobials need to penetrate the vesicle in which bacteria reside in the host cell, bringing additional challenges. For example, many bacteria resist the acidic environment of phagosomes. Thus, to eradicate these pathogens, antimicrobials must be active in low pH environments. Furthermore, many intracellular bacteria can adopt a non- or slow-replicating state that causes antibiotic failure, and the so-called persisters are phenotypically antibiotic-resistant. Consequently, antibiotic failure leads to chronic infections because of inadequate bacterial clearance. Exposure to lengthy antibiotic treatments is now considered a key factor contributing to the selection of multidrug-resistant intracellular pathogens.
Intracellular bacterial pathogens are difficult to reach by most clinically available antibiotics, which cannot penetrate or accumulate in the host infected cells. This leads to chronic infections, an increase in the therapeutic dose, and severe side effects. One of the key factors contributing to the selection of multidrug-resistant strains of intracellular pathogens is their ability to escape from antibiotics by infecting a host cell. Macrophages infected with intracellular bacteria are used by the pathogen as safe vehicles (e.g. Trojan horses) to disseminate through the body to secondary infection points. Moreover, most intracellular bacteria are becoming tolerant or resistant to the few antimicrobials available, leading to an increase in morbidity and mortality. During infection, exposure to common bacterial factors like lipopolysaccharide (LPS) leads to macrophage activation. While this state is effective against most common bacteria, intracellular bacterial pathogens have evolved to survive and grow inside macrophages, making treatment a formidable challenge. With the high economic costs of delivering a new antimicrobial to the clinic and their very limited lifetime and dosage, novel alternative approaches to treating intracellular bacterial infections are urgently needed.
The purpose of this research topic is to collect reports focused on providing new ways of battling intracellular pathogens. This includes combinatorial therapy, developing novel drug carriers, identifying novel antimicrobial compounds, activating the host's innate immunity, developing vaccines, identifying new bacteriophages or probiotics with antimicrobial effects, and other therapeutic strategies. We welcome submission of the following article types: Hypothesis and Theory, Methods, Mini Review, Opinion, Review, Original Research and Perspectives.
Intracellular survival protects bacterial pathogens from many antibiotics that need to cross host cellular membranes through diffusion or endocytosis to reach their targets. Because of this, more than two-thirds of the currently available antimicrobial treatments are ineffective against intracellular pathogens. In addition, intracellular pathogens reside in the cytosol or within different intracellular compartments. Therefore, antimicrobials need to penetrate the vesicle in which bacteria reside in the host cell, bringing additional challenges. For example, many bacteria resist the acidic environment of phagosomes. Thus, to eradicate these pathogens, antimicrobials must be active in low pH environments. Furthermore, many intracellular bacteria can adopt a non- or slow-replicating state that causes antibiotic failure, and the so-called persisters are phenotypically antibiotic-resistant. Consequently, antibiotic failure leads to chronic infections because of inadequate bacterial clearance. Exposure to lengthy antibiotic treatments is now considered a key factor contributing to the selection of multidrug-resistant intracellular pathogens.
Intracellular bacterial pathogens are difficult to reach by most clinically available antibiotics, which cannot penetrate or accumulate in the host infected cells. This leads to chronic infections, an increase in the therapeutic dose, and severe side effects. One of the key factors contributing to the selection of multidrug-resistant strains of intracellular pathogens is their ability to escape from antibiotics by infecting a host cell. Macrophages infected with intracellular bacteria are used by the pathogen as safe vehicles (e.g. Trojan horses) to disseminate through the body to secondary infection points. Moreover, most intracellular bacteria are becoming tolerant or resistant to the few antimicrobials available, leading to an increase in morbidity and mortality. During infection, exposure to common bacterial factors like lipopolysaccharide (LPS) leads to macrophage activation. While this state is effective against most common bacteria, intracellular bacterial pathogens have evolved to survive and grow inside macrophages, making treatment a formidable challenge. With the high economic costs of delivering a new antimicrobial to the clinic and their very limited lifetime and dosage, novel alternative approaches to treating intracellular bacterial infections are urgently needed.
The purpose of this research topic is to collect reports focused on providing new ways of battling intracellular pathogens. This includes combinatorial therapy, developing novel drug carriers, identifying novel antimicrobial compounds, activating the host's innate immunity, developing vaccines, identifying new bacteriophages or probiotics with antimicrobial effects, and other therapeutic strategies. We welcome submission of the following article types: Hypothesis and Theory, Methods, Mini Review, Opinion, Review, Original Research and Perspectives.
