Kingella kingae
              
            
            
              a Potentially Emerging Pathogen: a Comprehensive Review
            
            
              3
            
            
              From being almost an established pathogen among
            
            
              children,
            
            
              
                Kingella kingae
              
            
            
              has recently been reported to
            
            
              cause invasive infections in adults. A case of
            
            
              osteomyelitis pubis has been reported in an adult
            
            
              patient aged 66 years, with underlying end stage
            
            
              kidney disease and breast carcinoma (Wilmes et al.,
            
            
              2012).
            
            
              
                Prevalence and Colonization of
              
            
            
              
                
                  Kingella
                
              
            
            
              
                
                  kingae
                
              
            
            
              Considering the fact that there has been an increase in
            
            
              the incidences of invasive
            
            
              
                Kingella kingae
              
            
            
              infections
            
            
              both in children and in adults, a recent study carried
            
            
              out to assess the respiratory tract colonization and
            
            
              revealed that 97% of the pharyngeal samples were
            
            
              positive for
            
            
              
                Kingella kingae
              
            
            
              (Yagupsky, 2013). Sheep
            
            
              Blood agar with 2 mg/mL vancomycin (BAV) was
            
            
              used for the culture to increase the isolation rate which
            
            
              acts as a selective medium by inhibiting the growth of
            
            
              other Commensal gram positive bacteria (Yagupsky et
            
            
              al., 1995; Basmaci et al., 2012). Previous studies have
            
            
              confirmed that children below 6 months are not
            
            
              colonized with
            
            
              
                Kingella kingae
              
            
            
              and that the
            
            
              colonization rates vary among 6 months to 4 years
            
            
              (10%) children and school going children (4~14 years)
            
            
              (Goutzmanis et al., 1991). Yapupsky et al. (1995) in
            
            
              their study have noted that as the age increases the rate
            
            
              of colonization decreases with 3.2%, 1.5% and 0.8%
            
            
              colonization of
            
            
              
                Kingella kingae
              
            
            
              in respiratory
            
            
              secretions in children < 4 years old, 4~14 years and
            
            
              adults respectively (Yagupsky, 2013). A study from
            
            
              Switzerland, by Ceroni et al. (2012) which included
            
            
              431 young asymptomatic young children used
            
            
              real-time PCR for the detection of
            
            
              
                Kingella kingae
              
            
            
              from pharyngeal secretions and revealed a
            
            
              colonization rate of 8.1% (Ceroni et al., 2012).
            
            
              Previous studies have also confirmed the colonization
            
            
              of
            
            
              
                Kingella kingae
              
            
            
              in respiratory secretion among
            
            
              patients
            
            
              with microbiologically confirmed
            
            
              osteo-articular infections (Chometon et al., 2007).
            
            
              Studies have also revealed that
            
            
              
                Kingella kingae
              
            
            
              colonization was observed more in the oropharynx
            
            
              than in the nasopharynx confirming the fact that
            
            
              
                Kingella kingae
              
            
            
              occupies a rather narrow niche in the
            
            
              upper respiratory tract (Yagupsky et al., 2002).
            
            
              Reports have also indicated that there is an increased
            
            
              colonization and infection rates among day-care
            
            
              attendees,
            
            
              suggestive of overcrowding as a
            
            
              predisposing factor for person-to-person spread
            
            
              (Robinson, 2001).
            
            
              Studies on molecular typing with PFGE have
            
            
              confirmed that spread of
            
            
              
                Kingella kingae
              
            
            
              is associated
            
            
              with close mingling as seen among family members,
            
            
              playmates and community gatherings which should be
            
            
              considered as a predisposing factor for exposure
            
            
              (Yagupsky et al., 2009).
            
            
              
                Determinants of Colonization and Invasive
              
            
            
              
                Properties
              
            
            
              Microbial entry in to the human is very common but
            
            
              for it to cause infection/disease, the microbe should be
            
            
              able to adhere, adapt and invade. Pili are the surface
            
            
              projections present on the bacterial cell wall that help
            
            
              the organism to adhere. Studies have confirmed that
            
            
              
                Kingella kingae
              
            
            
              possesses type IV pili which play a
            
            
              key role in attachment to the respiratory epithelial
            
            
              cells and synovial cells (Kehl-Fie et al., 2008). Studies
            
            
              have also revealed certain genes (
            
            
              
                pilA1
              
            
            
              ,
            
            
              
                pilA2
              
            
            
              ,
            
            
              
                fimB
              
            
            
              ,
            
            
              
                pilS
              
            
            
              ,
            
            
              
                pilR
              
            
            
              ,
            
            
              
                pilC1
              
            
            
              ,
            
            
              
                pilC2
              
            
            
              ), that are coding for the
            
            
              expression of pili in
            
            
              
                Kingella kingae
              
            
            
              and have noted
            
            
              that strains isolated from colonized persons had pili
            
            
              and those isolated from invasive infections were
            
            
              non-piliated indicating that the process of piliation is
            
            
              self regulating and influenced by immune response
            
            
              (Kehl-Fie et al., 2010). Another protein, a trimeric
            
            
              autotransporter protein called
            
            
              
                Knh
              
            
            
              also helps
            
            
              
                Kingella
              
            
            
              
                kingae
              
            
            
              to firmly bind to the colonization sites (Porsch
            
            
              et al., 2012).
            
            
              
                Kingella kingae
              
            
            
              , has the property to form
            
            
              biofilms (ability of microorganisms to produce a
            
            
              polymeric matrix like substance surrounding them to
            
            
              evade immune response and antibiotics entry), that
            
            
              helps in colonization and periodic dispersion of
            
            
              bacteria to other parts of the host and enabling the
            
            
              bacteria to evade immune detection, dessication and
            
            
              antimicrobial action; it has also been noted that
            
            
              
                Kingella kingae
              
            
            
              has an anti-biofilm activity that
            
            
              prevents other bacterial colonization and there by
            
            
              establishing itself in the respiratory mucosa
            
            
              (Bendaoud et al., 2011). A toxin named RTX was
            
            
              identified as an exotoxin that is coded on the
            
            
              
                Kingella
              
            
            
              Molecular Pathogens