Misuse, overuse, and underuse of antimicrobials have become the main problem in the evolution of the resistance to an antibiotic. Over the last decade, the evolution and dissemination of antibiotic resistance has given rise to severe clinical and public health effects (Khan et al., 2019). The mechanisms resistance in Klebsiella pneumoniae to different antibiotic classes inclusive; changing of cell membrane permeability, efflux pump systems, production of antibiotic- inactivating enzymes, modification of metabolic pathways and a variation of antibiotic target sites (Verma et al., 2015). Certain mechanisms are either intrinsically encoded or acquired by the acquisition of resistance genes (Bialek Davenet et al., 2014). Among these mechanisms, efflux pump systems and enzymatic degradation play a significant role in increasing multidrug resistance (MDR) K. pneumoniae. K. pneumoniae was observed high develop antibiotic resistance due to the production of new enzymes that break down antimicrobials more easily than most bacteria (Venkatachalam et al., 2014). High term of β- lactamase as cephalosporinases and carbapenemases enzymes in K. pneumoniae command to multiplying resistant to β-lactam antibiotics. The cephalosporinases related to as ESBL (Venkatachalam et al., 2014). Usually, K. pneumoniae producing ESBL displayed resistance to β-lactam antibiotics like monobactams, penicillins and cephalosporins. K. pneumoniae carrying ESBL enzymes are considerably resistant to different class of antibiotics, included: chloramphenicol aminoglycosides and quinolones (Gruber et al., 2013). There are several mechanism of antibiotic resistance:

Efflux pumps

 Klebsiella pneumoniae expresses the efflux pump AcrAB, which contributes to the export of not only antibiotics (e.g., quinolones and β- lactams), but also host-derived antimicrobial agents, and AcrAB action as a determinant of K. pneumoniae resistance to host innate immune defenses. The inactivation of AcrAB not only leads to a multidrug resistance phenotype, but also to a reduced capacity to cause pneumonia in a murine model (Padilla et al., 2010). Efflux pump resistant mechanism is the most significant type of antibiotic resistance in order that the efflux pump can remove several antibiotics such as β-lactams, fluoroquinolones, aminoglycosides, and chloramphenicol. MDR K. pneumoniae isolated during antibiotic therapy are associated with the elevated expression for AcrAB or AcrAB-like pumps characterized that as a significant mechanism of antibiotic resistance (Coque et al., 2010). The AcrAB multidrug efflux system that in Klebsiella pneumoniae is encoded via the acrRAB operon. In this operon, acrB encode a periplasmic lipoprotein of 40 kDa, while acrR encodes the AcrAB repressor, anchored to the inner membrane, that bridges the outer and inner membranes and an integral membrane protein of 113.5 kDa with 12 membrane spanning α-helices, located in the cytoplasmic membrane, respectively (Domenech-Sanchez et al., 2001). AcrB join with TolC, an outer membrane protein that be owned to family of envelope proteins found in all Gram-negative bacteria and that is necessary for the package of a plethora of compounds (Eswaran et al., 2003). Some bacterial efflux pumps export not only antibiotics and other substances, such as tinctures and detergents, but also hostderived antimicrobial agents (Piddock, 2006).

Outer membrane

 porins Gram-negative bacteria generally possess an outer membrane that prevents the entry of foreign substances into the bacterial cell (Pagès et al., 2008). The outer membrane is made up of proteins defined as porins proteins that allow the hydrophilic pathways to gain certain compounds and nutrients, like antibiotics (Armand-Lefevre et al., 2003).

Klebsiella pneumoniae produces two major outer membrane porins – Ompk35 and Ompk36 through which hydrophilic molecules (e.g., nutrients and carbapenems / cephalosporins) spread into the bacteria (Tsai et al., 2013). Alterations in porins to the effect of the inflow of drugs and efflux during the movement through the membrane (Hu et al., 2015).

References

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Armand-Lefévre, L.; Leflon-Guibout, V.; Bredin, J.; Barguellil, F.; Amor, A.; Pagès, J. M. and Nicolas-Chanoine, M.-H. (2003). Imipenem Resistance in Salmonella enterica Serovar Wien Related to Porin Loss and CMY-4 β -Lactamase Production. Antimicrob. Agents Chemother., 47:1165 1168.

Bialek-Davenet, S.; Criscuolo, A.; Ailloud, F.; Passet, V.; Jones, L. and Delannoy-Vieillard, A.S. (2014). Genomic definition of hypervirulent and multidrug-resistant Klebsiella pneumoniae clonal groups. Emerging Infectious Dis. J., 20:1812-1820.

Coque, T.M ; Novais, A. and Carattoli, A. (2010). Dissemination of clonally related Escherichia coli strains expressing extended-spectrum beta- lactamase CTX-M-15. Emerging Infectious Dis., 14:195-200.

Domenech-Sanchez, A., S. Alberti, L. Martinez-Martinez, A. Pascual, I. Garcia, and V. J. Benedi. (2001). Abstr. 41st Intersci. Conf. Antimicrob. Agents Chemother., abstr.

Eswaran, J., C. Hughes, and V. Koronakis. (2003). Locking TolC entrance helices to prevent protein translocation by the bacterial type I export apparatus. J. Mol. Biol. 21:309–315.

Gruber, I.; Heudorf, U. and Werner, G. (2013). Multidrug-resistant bacteria in geriatric clinics, nursing homes, and ambulant care-prevalence and risk factors. Intern. J. Medical Microbiology, 303:405-409.

Hu, D.; Xi-wei X.; Wen-qi, S.; Ping, L. and Sangjie, Y. (2015). Characterization of multidrug-resistant and metallo β- lactamase- producing Klebsiella pneumoniae isolates from a paediatric clinic in China. Chinese Medical J., 121(17):1611-1616.

Khan, F.A.; Hellmark, B.; Ehricht, R.; Söderquist, B. and Jass, J. (2019). Related carbapenemase- producing Klebsiella isolates detected in both a hospital and associated aquatic environment in Sweden. European J. Clinical Microbiology and Infectious Dis., 37:2241-2251.

Padilla E, Llobet E, Domenech-Sanchez A, Martinez-Martinez L, Bengoechea JA, Alberti S. (2010). Klebsiella pneumoniae AcrAB efflux pump contributes to antimicrobial resistance and virulence. Antimicrob. Agents Chemother. 54(1), 177–183.

Pages, J.M.; Lavigne, J.P.; Leflon-Guibout, V.; Marcon, E.; Bert, F.; Noussair, L. and Nicolas-Chanoine, M.H. (2009). Efflux Pump, the Masked side of β-lactam resistance in Klebsiella pneumoniae clinical isolates. PLoS ONE; 4(3):177-180.

Piddock, L. J. (2006). Multidrug-resistance efflux pumps—not just for resistance. Nat. Rev. Microbiol. 4:629–636.

Tsai, S.S.; Huang, J.C.; Chen, S.T.; Sun, J.H. and Wang, C.C. (2013). Characteristics of Klebsiella pneumoniae bacteremia in community acquired and nosocomial infections in diabetic patients. Chang Gung Medical J., 33:532-539.

Venkatachalam, I.; Teo, J.; Balm, M.; Fisher, D.; Jureen, R. and Lin, R. (2014). Klebsiella pneumonia carbapenemase-producing enterobacteria in hospital, Singapore. Emerging Infection Dis., 18:1381-1383.

Verma, P.; Berwal, P.K.; Nagaraj, N.; Swami,S.; Jivaji, P. and Narayan, S. (2015). Neonatal sepsis: epidemiology, clinical spectrum, recent antimicrobial agents and their antibiotic susceptibility pattern. Intern. J. Contemporary Pediatrics, 2:176-180.

مواضيع ذات صلة

Neisseria meningitidis

الفرنسيسيلة التولارية Francisella tularensis

بكتريا الليسترية المستوحدة Listeria monocytogenes

عصيات الجمرة الخبيثة Bacillus anthracis

اليرسينية الطاعونية Yersinia pestis

البروسيلا Brucella وحمى مالطا Brucellosis

وتديات الخناق Corynebacterium diphtheria

SHIGELLA

بكتريا السل Mycobacterium tuberculosis

نيسيريا السيلان N.gonorrhoeae

بكتريا Borrelia burgdorferi

المرض المبقع Pinta