**2. Biofilm formation and antibiotic resistance**

Extracellular matrix is vital feature related to biofilm communities, it is surrounding the resident bacteria and it includes matrix proteins, lipid vesicles, exopolysaccharides and extracellular DNA (eDNA), whereas the 3 exopolysaccharides regarding *P. aeruginosa* biofilm matrix (alginate, Pel and Psl) [55]. Mainly, the biofilm includes bacterial derived exopolysaccharides which is protecting encapsulated bacteria from host immune cells as well as antibiotics [56]. In addition, biofilm are considered to be widespread in their nature and constituting a significant strategy carried out via microorganisms for surviving in often harsh conditions of environment. They might be effectives or leaving bad effect especially when created on medical devices or in industrial settings. Thus, studying the elimination and formation of biofilm is significant for a lot of discipline [57]. The ability of *P. aeruginosa* for creating biofilm, that were cells' communities which are encased in self produced extracellular matrix, protecting the cells from antibiotics as well as host immune [58]. Also, *P. aeruginosa* is considered opportunistic, nosocomial bacterial pathogen forming persistent infections because of creating protective communities, referred to as biofilm. Furthermore, biofilm is a significant virulence factor in *P. aeruginosa* and has considerable roles in antibiotic resistance as well as chronic burn wound infections [24], while the biofilm of *P. aeruginosa* are contributing to its survival on the abiotic and biotic surfaces and representing main clinical threat because of their increased tolerance to the antibiotics [59]. As soon as forming the biofilm, the bacteria embedded in it were recalcitrant to the anti-microbial treatment along with host immune defenses [60].

Biofilm have been specified as complex microbial communities which contain micro-colonies and surrounded by self-created extracellular polysaccharide matrix, while the biofilm matrix in *P. aeruginosa* includes 3 different exopolysaccharides: Pel, Psl and alginate. Also, the alginate can be defined as one of the polymers which contain α-L-guluronic acid and β-D-mannuronic acid with considerable roles in the structural stability as well as biofilm protection, while Psl has been specified as a polysaccharide includes repeating pentasaccharide, containing L-rhamnose,

D-glucose and D-mannose. Psl was significant in the start of the formation of the biofilm and biofilm structure protection. Pel is specified as the 3rd polysaccharide that exists in *P. aeruginosa* biofilm and was glucose rich [61]. Furthermore, the biofilm cells showing increased resistance to the environmental pressures like anti-microbial agents compared to their planktonic form [62]. Also, its populations undergoing characteristic evolutionary adaptation throughout chronic infection related to CF lung, involving decreased virulence factors' production, transition to biofilm related lifestyles, and the evolution regarding high level antibiotics resistance, whereas the populations of *P. aeruginosa* in the chronic CF lung infections generally showing increased phenotypic diversity, involving clinically significant characteristics like antibiotics resistance and toxin production, and such diversity was dynamic throughout the time, which will make precise treatment and diagnosis challenging [63].

## **3. Antibiotic resistance**

*P. aeruginosa* has been considered as a major cause related to nosocomial infections, also it is accountable for about 10% of all the hospital acquired infections in the world. It is still considered as one of the therapeutic challenges due to the high rates of mortality and morbidity related to it and the potential to develop drug resistance throughout the therapy. Also, standard antibiotic regimes against the *P. aeruginosa* were more and more unsuccessful due to the increase in drug resistance [64]. In addition, antibiotics resistance in the multiple strains related to *P. aeruginosa* was a clinical issue that is developing rapidly, while the definitions regarding multidrug resistance *P. aeruginosa* (MDRPA) was isolates resistant to minimum of 3 drugs from various antimicrobial categories, involving cephalosporinsand quinolones, aminoglycosides, carbapenems and anti pseudomonal penicillin were categorized as multidrug resistant. The development of antibiotic resistant bacteria in health-care is dangerous. With regard to health-care premises exactly ICUs were main microbial diversity sources. Recently, a few studies indicated that not just microbial diversity, yet also the drug resistant microbes majorly habitat in the ICUs.

Infections resulting from such organism were complicated to treat due to the existence of its innate resistance to various antibiotic types (Beta-lactam and penem group of antibiotics) as well as its capability for acquiring more resistance mechanism for a number of antibiotics classes, involving aminoglycosides, β-lactams and fluoroquinolones. With regard to molecular evolution microbes adopting many mechanisms for maintaining genomic plasticity [2], MDR isolates have been majorly specified via slow growth, cytotoxic type-III secretion system genotype, excellent biofilm forming capability, and the existence of more aminoglycoside modifying enzyme (AME) genes, non MDR isolates are re-sensitized following the inhibition regarding active efflux or improvement of membrane permeability, such target gene alteration along with the enzymatic drug modification that has been specified as the main quinolone mechanisms and aminoglycoside resistance in *P. aeruginosa* keratitis isolates [65]. Extensively drug-resistant *P. aeruginosa* (XDR-PA) that has been characterized as the strains remaining susceptible to only 1 or 2 antipseudomonal agent classes, became a serious issue because of a lack of effective anti-microbial treatment [66].

*P. aeruginosa* became resistant to a number of the antibiotics classes, which include the carbapenems, which have been viewed as reliable antibiotics for treating the multi-drug-resistant *P. aeruginosa* serious infections and have been viewed as a last-resort antibiotic therapy of the infections that have been caused by the carbapenem-resistant *Pseudomonas aeruginosa* has become more problematic, particularly

**13**

*Pseudomonas aeruginosa*: Diseases, Biofilm and Antibiotic Resistance

with increasing the carbapenem resistance. Carbapenem was commonly utilized for the directed or empirical treatments when a PA infection has been suspected as a result of its natural resistance towards numerous antibiotic types [67]. None-theless, the recent data from National Antimicrobial Resistance Surveillance, Thailand (NARST), has shown an increasing CRPA trend, from about 15% of infections in the period 2000–2005 to 30% in the period 2009–2013. The rate of the CRPA which is related healthcare-associated infection (HAI) increased in past year all over the

*Pseudomonas aeruginosa* isolates have intrinsic resistance to the majority of the antimicrobials through the chromosomal AmpC cephalosporinases as well as low permeability to the antimicrobials, and can be accumulating extra resistance determinants through acquiring elements of the mobile genetics. *Pseudomonas aeruginosa* is of a large genome (i.e. higher than 6 MB), a high proportion of the regulatory genes and a set of the virulence determinants. The capability of using several mechanisms, which includes a decrease in the external membrane permeability, produces antibiotic degradative enzymes, efflux pump expression, production of the alginate and resistance gene transfer, the bacteria enabled showing a high resistance level to most of the utilized antibiotics [69]. Several recent researches have reported alternative and complementary options of the treatment to the infections of the combat *Pseudomonas aeruginosa*. Quorum sensing inhibitors, probiotics, phages, vaccine antigens, antimicrobial peptides, and anti-microbial nano-particles

have the possibility of acting against the drug resistant strains [64].

There is no 'conflict of interest' for this work.

Hussein Al-Dahmoshi\*, Raad D. Al-Obaidi and Noor Al-Khafaji

\*Address all correspondence to: dr.dahmoshi83@gmail.com

provided the original work is properly cited.

Biology Department, College of Science, University of Babylon, Hilla, Iraq

© 2020 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium,

The current review conclude the implication of *P. aeruginosa* in arrays of diseases especially RTIs, UTIs and wound infections. The widespread of it may be due to their adaptation to different environmental conditions along with virulence traits especially biofilm formation and intrinsic and acquired antibiotic resistance

*DOI: http://dx.doi.org/10.5772/intechopen.95251*

world [68].

**4. Conclusion**

strategies.

**Conflict of interest**

**Author details**

*Pseudomonas aeruginosa*: Diseases, Biofilm and Antibiotic Resistance *DOI: http://dx.doi.org/10.5772/intechopen.95251*

with increasing the carbapenem resistance. Carbapenem was commonly utilized for the directed or empirical treatments when a PA infection has been suspected as a result of its natural resistance towards numerous antibiotic types [67]. None-theless, the recent data from National Antimicrobial Resistance Surveillance, Thailand (NARST), has shown an increasing CRPA trend, from about 15% of infections in the period 2000–2005 to 30% in the period 2009–2013. The rate of the CRPA which is related healthcare-associated infection (HAI) increased in past year all over the world [68].

*Pseudomonas aeruginosa* isolates have intrinsic resistance to the majority of the antimicrobials through the chromosomal AmpC cephalosporinases as well as low permeability to the antimicrobials, and can be accumulating extra resistance determinants through acquiring elements of the mobile genetics. *Pseudomonas aeruginosa* is of a large genome (i.e. higher than 6 MB), a high proportion of the regulatory genes and a set of the virulence determinants. The capability of using several mechanisms, which includes a decrease in the external membrane permeability, produces antibiotic degradative enzymes, efflux pump expression, production of the alginate and resistance gene transfer, the bacteria enabled showing a high resistance level to most of the utilized antibiotics [69]. Several recent researches have reported alternative and complementary options of the treatment to the infections of the combat *Pseudomonas aeruginosa*. Quorum sensing inhibitors, probiotics, phages, vaccine antigens, antimicrobial peptides, and anti-microbial nano-particles have the possibility of acting against the drug resistant strains [64].
