Klebsiella is a gram negative, rod-shaped, facultative anaerobe, possessing the characteristics of being non-sporulating, fermenting and non-motile microbe (Vading 2016). The cultural characteristics show mucoid colonies on agar medium and are lactose fermenter (Martin, Bachman et al. 2018). It belongs to the family Enterobacteriaceae, a normal flora of human gut but an opportunistic pathogen (Kaspersen 2015). This family falls in phylum Proteobacteria, class Gamma proteobacteria and order Enterobacteriales (Bennett, Dolin et al. 2014). The members of this family are Escherichia coli, Klebsiella spp., Proteus spp., Citrobacter spp., Enterobacter spp., Salmonella spp., Serratia spp., and Shigella spp. These microbes play a role in both community and hospital acquired infections (Tailor 2011). It can gain or losing a gene by means of lateral gene transfer, thus showing plasticity in nature. Since it has a characteristic of high metabolic adaptability, it can survive in various environmental conditions. Usually, Klebsiella colonizes in intestine and upper respiratory tract of humans and other animals too, but it may also be present in water, soil, insects and plants (Vading 2016). The route of transmission of Klebsiella pneumoniae is through hospital equipment to the intestines of patients (Jumaa and Chattopadhyay 1992, Ransjö, Good et al. 1992) and skin of hospital staff (Montgomerie 1979, Podschun and Ullmann 1998, Mills, Talati et al.
2016). In many animals, Klebsiella pneumoniae is responsible for invasive disease (Twenhafel, Whitehouse et al. 2008, Jang, Wheeler et al. 2010) and mostly found in food sources (Manges 2015, Moradigaravand, Martin et al. 2017).
Pakistan faces a critical problem related to hospital-acquired infections due Klebsiella spp. Many individuals in Pakistan encounter with Klebsiella pneumoniae infections causing the healthcare settings or hospitals to become overly crowded which leads to many mortality and morbidity cases. The frequency of cases causes poor hygienic environment (Ahmed, BAQIR et al. 2002, Shahid, Malik et al. 2008, Shaikh, Devrajani et al. 2008, Afzal 2017).
Klebsiella pneumoniae is known to have plasmids and mobile elements which result in a variety of specific genomic variation among its strains (Lai, Yang et al. 2000, Wu, Li et al. 2009, Zhao, Bai et al. 2010). Klebsiella pneumoniae possesses genes for capsules (k2A, magA, wcaG), lipopolysaccharides (wabG, uge, ycfM), for iron acquisition systems (iutA, iroN, entB), hypermucoviscosity (magA, rpmA) and for adhesins (fimH, mrkD, kpn). These factors aid in evading the host defense mechanisms (Sebghati, Korhonen et al. 1998, Mamlouk, Boubaker et al. 2006, Yu, Ko et al. 2006, Yu, Fung et al. 2007, Yu, Ko et al. 2008, Hartman, Selby et al. 2009, Turton, Perry et al. 2010, Guiral, Bosch et al. 2011, El Fertas-Aissani, Messai et al. 2013).
Many bacteria produce iron-chelating molecules for iron acquisition known as siderophores. These molecules possess high affinity and have low molecular weight (Martin, Bachman et al. 2018).
Production of siderophores occurs specifically in cytoplasm and transported to extracellular area. Both the inner and outer membrane proteins, namely, TolC, are involved in the export of siderophores (Garénaux, Caza et al. 2011, Porcheron, Garénaux et al. 2013). There are various siderophores produced by Klebsiella pneumoniae (Holden and Bachman 2015), most commonly enterobactin (Ent) encoded in its core genome (Martin, Bachman et al. 2018). These siderophores also play a key role in developing inflammation and the spread of bacteria to make iron available for the replication of Klebsiella pneumoniae (Holden, Breen et al. 2016, Martin, Bachman et al. 2018). There are three known siderophores secreted by Klebsiella pneumoniae, namely, yersiniabactin, enterobactin, and aerobactin (Lawlor, O'Connor et al. 2007, Bachman, Oyler et al. 2011), in which yersiniabactin is involved in causing human invasive respiratory tract infections (Holt, Wertheim et al. 2015). Whereas in extreme situations when iron is insufficient, enterobactin plays its role in the survival of Klebsiella pneumoniae cells (Lawlor, O'Connor et al. 2007). It has been observed in mouse and in-vitro studies that aerobactin aids in developing invasive infections caused by Hypervirulent Klebsiella pneumoniae (HvKP) (Russo, Olson et al. 2015, Gomez-Simmonds and Uhlemann 2017). It has been observed that > 90% of the enterobacterial isolates showed the production of enterobactin (Raymond, Dertz et al. 2003).
Antibiotic resistance occurs through many mechanisms deployed by Klebsiella pneumoniae, such as aminoglycoside-modifying enzymes (AMEs), extended-spectrum β-lactamases (ESBLs), plasmid-mediated quinolone resistance (PMQR) genes, 16S rRNA methyltransferase (16SRMTase) and carbapenemases (Findlay, Hopkins et al. 2015, Buruk, Öztel et al. 2016, Afzal 2017).
Literature reveals that there were cases of unusual community-acquired Klebsiella pneumoniae infection reported from Taiwan in mid 80s and 90s which showed that the infected individuals had no hepatobiliary disease history, but the community-acquired pyogenic liver abscesses (CA-PLA) were observed in them with a capability to disseminate in other parts of body (Liu, Cheng et al. 1986, Liu, Yen et al. 1991, Wang, Liu et al. 1998). These cases were studied first in countries such as Taiwan, Korea, Vietnam and Japan but significant cases of such infection were observed later in North America (Lederman and Crum 2005, Keynan, Karlowsky et al. 2007, Nadasy, DomiatiSaad et al. 2007, Pastagia, Arumugam et al. 2008, Frazee, Hansen et al. 2009, McCabe, Lambert et al. 2010, Fierer, Walls et al. 2011, Pomakova, Hsiao et al. 2012), South America (Vila, Cassata et al. 2011), the Caribbean (Doud, Grimes-Zeppegno et al. 2009), Europe (Gunnarsson, Brandt et al. 2009, Sobirk, Struve et al. 2010, Decré, Verdet et al. 2011), the Middle East (Turton, Englender et al. 2007, Enani and El-Khizzi 2012), Australia (Turton, Englender et al. 2007), Africa and South Africa (Yu, Hansen et al. 2007, Decré, Verdet et al. 2011). A new type of Klebsiella pneumoniae was isolated, capable of developing infections in an ambulatory and healthy individual (Fang, Lai et al. 2007, Yu, Hansen et al. 2007, Decré, Verdet et al. 2011, Pomakova, Hsiao et al. 2012). This new strain was able to cause infection endophthalmitis and meningitis, and showed metastatic spread in body (Liu, Yen et al. 1991). It has been observed that hypervirulent Klebsiella pneumoniae infection begins when the bacterial cells colonize (Montgomerie 1979) specially in host gastrointestinal (GI) tract, but they also colonize in oropharynx or skin (Shon, Bajwa et al. 2013).
In this study Pan Genomic Analysis was performed and the analysis reveals that the bacteria is vibrant and adopted changes in the genomic architecture in response to the various environmental factor.