The intracellular phase of extracellular respiratory tract bacterial pathogens and its role on pathogen-host interactions during infection

Abstract

Purpose of review An initial intracellular phase of usually extracellular bacterial pathogens displays an important strategy to hide from the host's immune system and antibiotics therapy. It helps the bacteria, including bacterial pathogens of airway diseases, to persist and eventually switch to a typical extracellular infection. Several infectious diseases of the lung are life-threatening and their control is impeded by intracellular persistence of pathogens. Thus, molecular adaptations of the pathogens to this niche but also the host's response and potential targets to interfere are of relevance. Here we discuss examples of historically considered extracellular pathogens of the respiratory airway where the intracellular survival and proliferation is well documented, including infections by Staphylococcus aureus, Bordetella pertussis, Haemophilus influenzae, Pseudomonas aeruginosa, and others. Recent findings Current studies focus on bacterial factors contributing to adhesion, iron acquisition, and intracellular survival as well as ways to target them for combatting the bacterial infections. Summary The investigation of common and specific mechanisms of pathogenesis and persistence of these bacteria in the host may contribute to future investigations and identifications of relevant factors and/or bacterial mechanisms to be blocked to treat or improve prevention strategies.

The polyamino-isoprenyl potentiator NV716 revives disused antibiotics against Gram-negative bacteria in broth, infected monocytes, or biofilms, by disturbing the barrier effect of their outer membrane

“…In addition to resistance, intracellular survival and biofilm formation also contribute to antibiotic treatment failure (11,12). Although considered essentially as extracellular pathogens, E. coli, K. pneumoniae and A. baumannii may also behave as opportunistic intracellular organisms.…”

Pathogenesis of nontypeable Haemophilus influenzae infections in chronic suppurative lung disease

“…Relatively little is known of how NTHi survives and traffics within this environment. Transcriptional factors, such as the ferric uptake regulator cassette which regulates the expression of multiple genes controlling the uptake and utilization of iron, and IgaB that cleaves lysosomal‐associated membrane protein‐1, appear to be important, and NTHi can survive for at least 72‐h inside AECs 90,91 …”

“…Transcriptional factors, such as the ferric uptake regulator cassette which regulates the expression of multiple genes controlling the uptake and utilization of iron, and IgaB that cleaves lysosomal-associated membrane protein-1, appear to be important, and NTHi can survive for at least 72-h inside AECs. 90,91 Furthermore, lung explant cultures from COPD and CF patients undergoing transplantation for end-stage lung disease revealed that despite negative sputum and lung tissue cultures, NTHi was detected widely throughout the lung parenchyma and lower airway tissue sections by immunoperoxidase staining and polymerase chain reaction assays. 85 While most NTHi were detected in clusters in extracellular and paracellular locations, in CF patients they were found within macrophages too.…”

Use of niosomes for the treatment of intracellular pathogens infecting the lungs

“…Pathogens responsible for lung diseases have been classified on how they replicate either inside or outside the host cell as extracellular, obligated intracellular, or facultative intracellular. Intracellular pathogens can hide or escape from the immune system and antibiotics by surviving the host's defense mechanism, cellular adhesion to invade the host, and adapting to the intracellular environment of the host (Lamberti & Surmann, 2021).…”