## 5 Other Therapeutic Approaches
### Vaccines  
Antibiotic-resistant species also evolve to colonize and evade host immunity. The approach of targeting biofilms using vaccines poses numerous difficulties in targeting bacterial biofilms since vaccines are specific to a particular microorganism and show large variability in the expression of vaccine-targeted epitopes [4]. Nevertheless, recently several conjugative vaccines have been formulated that target typically conserved EPS components. Staphvax is a conjugative vaccine that comprises polysaccharides and protein that acts on capsular polysaccharide serotypes (CP5 and CP5) in _S. aureus_[135]. The DNABII family of  
\begin{table}
\begin{tabular}{c c c c c} \hline \hline
**Type of Therapy** & **Target** & **Biofilm** & **Type of Assay** & **References** \\ \hline Bacteriophage therapy & EPS polysaccharide & _S. aureus_ & in vitro & [128] \\ Vaccine (Staphvax) & capsular polysaccharide serotypes (CP5 and CP5) & _S. aureus_ & phase III clinical trials & [135] \\ \hline CRISPR/Cas & _lux5_ and _fimH_ genes & _E. coli_ & in vitro & [132; 133] \\ \hline CRISPR/Cas & ompA & _C. neteri_ & in vivo & [134] \\ \hline Photodynamic therapy & EPS & _S. aureus_ & in vitro & [12] \\ \hline Virus like particles & agr QS system & _S. aureus_ & in vivo & [135; 136] \\ \hline Vaccine & pili-S and integration host factor (IHF) & _H. influenzae_ & in vivo & [137] \\ \hline Catalytic antimicrobial robots & kill cells and detach biofilms & _S. mutans_ & in vitro & [138] \\ \hline Nitric oxide-releasing nanoparticles & N/A & _S. aureus_ & in vivo & [139] \\ \hline ArikayceTM & inhibition of protein synthesis & _M. avium_ & phase III clinical trials & [140] \\ \hline FluidsomesTM & inhibition of protein synthesis & _P. aeruginosa_ & Phase II clinical trials & [140] \\ \hline Calcium fluoride nanoparticles & various cellular processes & _S. mutans_ & in vitro and in vivo & [141] \\ \hline \hline \end{tabular}
\end{table}
Table 6: Some therapeutic approaches effective against biofilms.  
DNA-binding proteins, which consists of the integration host factor (IHF), gives structural integrity to eDNA in biofilms [142]. Studies confirm that antibodies against _E. coli_ IHF can bind to DNABII in many bacterial species and destabilize biofilms by releasing individual bacterium. DNA II, when combined with antibiotic therapy, showed a synergistic effect in treating biofilms of numerous bacterial species such as oral bacteria [143], UPEC [144], _P. aeruginosa_[145], and _S. aureus_[146; 147] in a murine lung infection model [142]. The next approach is to combine DNABII antibodies with vaccines. A study using IHF and recombinant soluble type IV pili co-administered with an adjuvant in an animal model of otitis media with nontypeable _Haemophilus influenzae_ (NTHi) showed early NTHi eradication and prevention of disease [137]. Alternatively, to detect immunogenic mimic of a QS peptide, the usage of Virus-like Particles (VLPs) is increasing. Some results indicate that a diagnosis of VLP-based epitope for the development of a vaccine that targets _agr_ signal disruption could be effective against _S. aureus_ SSTI [135; 136]. Better molecular identification of biofilm-associated genes can advance vaccines development against bacterial infections in the future [135].