**4. The concern**

*Pseudomonas aeruginosa - An Armory Within*

mortality associated with this disease condition are due to thickened lung secretions and subsequent creation of hypoxia and secondary infections predominantly by opportunistic pathogens. Bacteria such as *Pseudomonas aeruginosa*, *Staphylococcus aureus*, and *Burkholderia cepacia* complex have been in the limelight as the pathogens that affect CF patients with progression of lung disease ultimately leading to mortality. Interestingly, recent developments in high-throughput genomic techniques revealed the presence of several other bacterial species, which were hardly identified using conventional microbiological techniques. Enteric bacteria, such as *Prevotella*, *Bacteroides*, *Fusobacterium*, *Mycoplasma*, *Ralstonia*, *Veillonella*, etc., which do not normally appear in the laboratory cultures were identified and were found to have an impact on the CF microbiome [4]. This fluctuation in the CF microbiome may be due to transition of atypical species toward chronic mode of infection through formation of biofilms, dormancy, small colony variants, etc. The immunocompromised nature of CF patients predisposes them to a variety of infections, thereby increasing the need for antibiotics, alone or in combination, on a daily basis, at milligram levels. Such a continuous antibiotic pressure drives evolution of lung pathogens through the downregulation of acute-mode virulence factors in order to avoid unnecessary energy loss and expression of regulons associated with chronic mode of infection/colonization. Though the CF microbiome has been shown to consist of several species of bacteria, *P. aeruginosa* becomes the predominating one during the course of chronic colonization in the CF lung, thereby increasing its significance when considering appropriate treatment strategy [5]. Apart from the abovementioned bacterial species in the CF microbiome, mycobacteria, in general, are widespread organisms except tuberculosis (*Mycobacterium tuberculosis*) and leprosy (*M. leprae*) pathogens which are obligate parasites always in need of a host. These bacteria are often involved in asymptomatic infections, are highly fastidious organisms showing resistance to antibiotics, and are able to survive for long periods in acids, alkali, detergents, etc. Non-tuberculous mycobacteria constitute all the other mycobacteria gaining importance in respiratory infections including the one resembling tuberculosis. Practically, overgrowth of pseudomonads and other predominant bacterial species in the lung makes it difficult to understand the existence of atypical bacteria in the case of CF lung infections. The inherent slow growth rate of mycobacteria adds to failures in preliminary detection of these bacteria. Once identified it requires a prolonged treatment regime for several months with combined antibiotics, which add stress to the CF lung environment, thereby resulting in a progressive deterioration of lung function with consequent emergence of resistant pathogens. Dominance by *P. aeruginosa* or few known predominant bacterial species in the CF lung is clinically beneficial in the sense that these outnumbered species may offer protection against more pathogenic species

Normally, tuberculosis is rare among CF patients, and it was found to complicate the CF disease condition. It is also interesting to know that the CF disease condition will not support growth of TB mycobacteria (*Mycobacterium tuberculosis*) and the risk of TB in these patients is high in areas with high prevalence. In addition, other chronic illnesses such as poorly controlled diabetes were considered as an additional

Among non-typical mycobacteria (NTM), *M. abscessus* is considered the most clinically virulent species. Isolation of NTM is common in CF patients before lung transplantation as revealed by data from a large US center. However, reports

**2**

such as mycobacteria [6].

**3. A friend or a foe?**

risk factor among CF patients.

Huge genetic repertoire and mosaic genome structure of *P. aeruginosa* make it a versatile opportunistic pathogen in nosocomial settings, particularly in conditions involving burns and wounds, meningitis, endocarditis, and microbial keratitis. Interestingly, *P. aeruginosa* displays a common phenotype in the CF lung irrespective of the genetic content, which includes mucoidy, lipopolysaccharide modifications, lack of flagella and pili, upregulated antibiotic efflux, etc. New forms of emerging resistance in bacteria spread rapidly by intra- and interspecies acquisition of genetic content from the environment where community biofilms are common. In addition to being a threat to public health, highest resistance rates correlate with highest per capita antibiotic consumption of a nation.
