**2.2 Intra-abdominal, pelvic and soft tissue infections**

ENT are often recovered as a component of mixed microbial flora from cultures of pelvic, soft tissues and intra-abdominal infections. They rarely cause monomicrobial infections at these sites. Enterococcal bacteremia is accompanied with intra-abdominal and pelvic abscesses and wounds; this is the reason why many clinicians prescribe antibiotic regimens for infections at these sites [14, 16, 17]. Moreover, ENT are frequently found in cultures from foot ulcers, decubiti and in diabetics in association with osteomyelitis [15]. Tigecycline, a semi synthetic, bacteriostatic in nature analogue of TET is active against many Gram negative (G −ve) and G +ve bacteria has been used use for the treatment of skin, intra-abdominal and soft tissue infections [18].

## **2.3 Bacteremia**

Incidence of enterococcal blood stream infections are rising day by day [19]. Starting from 6th position in early 80's, ENT is now the 2nd most common cause of health care associated bacteremia [8]. Bacteremia is designated as a major cause of mortality with *Enterococcus* spp. being the third and fourth most common etiological agent of blood stream infections in U.S and Denmark, respectively [20–22]. Genitourinary tract, intra-abdominal, biliary sources, soft tissues infections and indwelling central lines are the common sources of bacteremia from which ENT are isolated as a polymicrobial component [17]. Although enterococcal bacteremia occurs in patients with underlying immunity and illnesses, it rarely affects distant organs or cause metastatic abscesses. Usage of inappropriate antibiotics or late treatment is associated with excess mortality [19]. However, some studies found no decrease in mortality with appropriate antibiotic treatment [23, 24], while some revealed a better outcome after using appropriate antibiotics both for vancomycin and high-level gentamicin resistant enterococci [25, 26].

#### **2.4 Endocarditis**

Endocarditis is one of the major enterococcal infections for which antibiotic treatment is difficult because of enterococci's intrinsic resistance to many antibiotics. First case report of endocarditis with details of clinical and pathological description of a strain called *Micrococcus zymogens* (*Enterococcus faecalis*) was published in 1899 [27]. Since then this species is responsible for 8–17% of all infective endocarditis (IE) cases affecting mainly elderly patients with prosthetic heart valve, degenerative heart valve diseases, urinogenital or GIT infections leading to bacteremia and becoming third most frequent etiologic agent of both native and prosthetic valve IE [28–30]. In certain cases, dual antibiotic therapy including aminoglycoside (preferably gentamicin) and cell-wall synthesis inhibitor (vancomycin or β-lactam) is required for IE therapy.

American Heart Association (AHA) and European Society of Cardiology (ESC) recommends 4 to 6 weeks of combined antibiotic treatment with success rate of 80%. Due to nephrotoxic effects of long-term aminoglycoside usage, Danish guidelines on endocarditis treatment endorsed aminoglycoside usage but for 2 weeks only [30]. In case of VRE and HLGR enterococcal IE, surgery remains the only option to remove the infected valve [15]. Among *Enterococcus* spp., *E. fl* was thought to be the most common causative agent of endocarditis infecting mostly older persons as compared to women [31, 32] but recently a more problematic MDR strain of

**113**

**3.2 Catalase (EC 1.11.1.6)**

*The Genus* Enterococcus *and Its Associated Virulent Factors*

*E. fm* belonging to well characterized hospital-associated clade was also identified as a cause of IE. The strains of *E. fm* has high resistance against first line antibiotics (i.e., MIC >64 mg/L ampicillin and vancomycin) due to which their application in curing IE is obsolete [33, 34]. In response to this, AHA recommends Quinupristindalfopristin (Q/D; 30% Streptogramin B and 70% A) and linezolid as alternate to treat MDR *E. fm* IE [35]. In fact, many reports suggest better efficacy of Q/D (24 g/day) when use in combination with imipenem, levofloxacin, doxycycline, rifampicin, high-dose ampicillin [36, 37]. Two main and critical steps in the pathogenesis of IE are attachment to tissues and production of biofilm. Biofilm associated proteins which facilitates occurrence of IE includes aggregation substance protein, i.e., *Asc10* [38], microbial surface components recognizing adhesive matrix molecules (MSCRAMM) proteins *ace* for *E. fl* [39] and *acm* for *E. fm* [40], *esp* and its homolog in *E. fm*, *espfm* [41, 42], endocarditis and biofilm associated pili of *E. fl*, i.e., *ebp* [42–44]. The main complication of enterococcal IE is heart failure occurring in half of the patients. Moreover, MDR *E. fm* is also an important factor in increasing epidemiology of enterococcal IE because >90% of *E. fl* are susceptible to ampicillin

**3. Pathogenesis and virulence associated with enterococci**

**3.1 Gelatinase (***gelE***), serine protease (***sprE***) and** *fsr* **regulator**

by processing of C-terminal gelatinase protein [57, 58].

secreted by ENT that damage the tissues [46].

Virulence factors are potential traits that define the pathogenesis of most infections which involves a series of events namely, colonization, adhesion to the host's cells, tissue invading and resistance to non-specific defensive mechanisms. Researchers are encouraged to characterize the factors involved in etiology of infections caused by pathogenic ENT in immunocompromised or impaired immunity patients. Two major classes of virulent factors have been well characterized: (1) surface factors that promote colonization in host cells, and (2) protein and peptides

Gelatinase is a zinc metalloprotease expressed extracellularly and hydrolyze gelatin, collagen and casein [47]. It is proved to be a full virulence factor expressed in mouse model of peritonitis, endocarditis [48, 49], endophthalmitis [50], in nematode [51] and in vitro translocation [52]. It is encoded by *gelE* and *sprE* operon and expressed in regulation by a quorum sensing system encoded by the *fsr* locus [53]. The *fsr* locus (*E. fl* regulator) is a well characterized locus containing *fsrA*, *fsrB*, *fsrC* and *fsrD* genes which is homologs to staphylococcal *agrBCA* loci [54]. A signaling peptide in *fsrB* liberates gelatinase biosynthesis activating pheromone (GBAP) peptide by auto-processing and a quorum sensing system. *gelE* and *sprE* genes are induced when GBAP accumulates from exponential to stationary phase. *Fsr* regulon is present above the *sprE* and *gelE* and encode a serine protease and gelatinase, respectively [55]. Possible molecular mechanism behind the expression of *gelE* and *sprE* is shown in **Figure 4** [56]. Epidemiological data suggests the involvement of *fsr* locus and gelatinase in virulence traits, like adhesion capacity (biofilm) established

Catalase is a renowned enzyme present in all three domains of life. It catalyzes the decomposition of hydrogen peroxide (HP) to water and oxygen, protecting the cell from oxidative damage of HP. HP is a reactive oxygen species (ROS) in

*DOI: http://dx.doi.org/10.5772/intechopen.89083*

and vancomycin [45].

*The Genus* Enterococcus *and Its Associated Virulent Factors DOI: http://dx.doi.org/10.5772/intechopen.89083*

*Microorganisms*

ated pathogen [15].

**2.3 Bacteremia**

**2.4 Endocarditis**

is required for IE therapy.

that 15% of UTIs occur in ICU setting with VRE being the major health care associ-

ENT are often recovered as a component of mixed microbial flora from cultures of pelvic, soft tissues and intra-abdominal infections. They rarely cause monomicrobial infections at these sites. Enterococcal bacteremia is accompanied with intra-abdominal and pelvic abscesses and wounds; this is the reason why many clinicians prescribe antibiotic regimens for infections at these sites [14, 16, 17]. Moreover, ENT are frequently found in cultures from foot ulcers, decubiti and in diabetics in association with osteomyelitis [15]. Tigecycline, a semi synthetic, bacteriostatic in nature analogue of TET is active against many Gram negative (G −ve) and G +ve bacteria has been used

use for the treatment of skin, intra-abdominal and soft tissue infections [18].

Incidence of enterococcal blood stream infections are rising day by day [19]. Starting from 6th position in early 80's, ENT is now the 2nd most common cause of health care associated bacteremia [8]. Bacteremia is designated as a major cause of mortality with *Enterococcus* spp. being the third and fourth most common etiological agent of blood stream infections in U.S and Denmark, respectively [20–22]. Genitourinary tract, intra-abdominal, biliary sources, soft tissues infections and indwelling central lines are the common sources of bacteremia from which ENT are isolated as a polymicrobial component [17]. Although enterococcal bacteremia occurs in patients with underlying immunity and illnesses, it rarely affects distant organs or cause metastatic abscesses. Usage of inappropriate antibiotics or late treatment is associated with excess mortality [19]. However, some studies found no decrease in mortality with appropriate antibiotic treatment [23, 24], while some revealed a better outcome after using appropriate antibiotics both for vancomycin

Endocarditis is one of the major enterococcal infections for which antibiotic treatment is difficult because of enterococci's intrinsic resistance to many antibiotics. First case report of endocarditis with details of clinical and pathological description of a strain called *Micrococcus zymogens* (*Enterococcus faecalis*) was published in 1899 [27]. Since then this species is responsible for 8–17% of all infective endocarditis (IE) cases affecting mainly elderly patients with prosthetic heart valve, degenerative heart valve diseases, urinogenital or GIT infections leading to bacteremia and becoming third most frequent etiologic agent of both native and prosthetic valve IE [28–30]. In certain cases, dual antibiotic therapy including aminoglycoside (preferably gentamicin) and cell-wall synthesis inhibitor (vancomycin or β-lactam)

American Heart Association (AHA) and European Society of Cardiology (ESC) recommends 4 to 6 weeks of combined antibiotic treatment with success rate of 80%. Due to nephrotoxic effects of long-term aminoglycoside usage, Danish guidelines on endocarditis treatment endorsed aminoglycoside usage but for 2 weeks only [30]. In case of VRE and HLGR enterococcal IE, surgery remains the only option to remove the infected valve [15]. Among *Enterococcus* spp., *E. fl* was thought to be the most common causative agent of endocarditis infecting mostly older persons as compared to women [31, 32] but recently a more problematic MDR strain of

**2.2 Intra-abdominal, pelvic and soft tissue infections**

and high-level gentamicin resistant enterococci [25, 26].

**112**

*E. fm* belonging to well characterized hospital-associated clade was also identified as a cause of IE. The strains of *E. fm* has high resistance against first line antibiotics (i.e., MIC >64 mg/L ampicillin and vancomycin) due to which their application in curing IE is obsolete [33, 34]. In response to this, AHA recommends Quinupristindalfopristin (Q/D; 30% Streptogramin B and 70% A) and linezolid as alternate to treat MDR *E. fm* IE [35]. In fact, many reports suggest better efficacy of Q/D (24 g/day) when use in combination with imipenem, levofloxacin, doxycycline, rifampicin, high-dose ampicillin [36, 37]. Two main and critical steps in the pathogenesis of IE are attachment to tissues and production of biofilm. Biofilm associated proteins which facilitates occurrence of IE includes aggregation substance protein, i.e., *Asc10* [38], microbial surface components recognizing adhesive matrix molecules (MSCRAMM) proteins *ace* for *E. fl* [39] and *acm* for *E. fm* [40], *esp* and its homolog in *E. fm*, *espfm* [41, 42], endocarditis and biofilm associated pili of *E. fl*, i.e., *ebp* [42–44]. The main complication of enterococcal IE is heart failure occurring in half of the patients. Moreover, MDR *E. fm* is also an important factor in increasing epidemiology of enterococcal IE because >90% of *E. fl* are susceptible to ampicillin and vancomycin [45].
