## 7 The Concept of the 'Effector Strain'
\begin{table}
\begin{tabular}{c c c c c c c c} \hline \hline
**Baseline** & **Type of Study** & **Patient** & **Baseline** & **Study Groups** & **Treatment** & **Probiotic** & **Strain** & **Results** \\
**Condition** & **Type of Study** & **Type** & **Condition** & **Study Groups** & **Treatment** & **Strains** & **Strain** & **Scenarios** \\ \hline \multirow{9}{*}{\begin{tabular}{c} [PERSON]- \\ tri et al. (2020) [88] \\ \end{tabular} } & Randomized, & & & & \(1\times 3\) g of placebo & & & \\  & double-blind, & Preschool & & & & \(1\times 3\) g of probiotic & & \\  & placebo- & children & Healthy & & milk powder in & & \\  & controlled & (1-5) & Caries & Group I (\(n=86\)) & 50 mL of milk for & & \\  & with 3 & years old) & & & Group II (\(n=89\)) & 7 days/week for & & \\  & parallel arms & & & & Group II (\(n=89\)) & 7 days/week for & & \\  & & & & Group II (\(n=93\)) & 6 months & & \\  & parallel arms & & & & Group III (\(n=93\)) & 1 \(\times 3\) g of probiotic & & \\  & parallel arms & & & & & \(50\) mL of milk for & & \\  & & & & & & \(3\) days/week \(\sim 3\) g of & & \\  & & & & & placebo milk powder & & \\  & & & & & in 50 mL of milk for & & \\  & & & & & & \(4\) days/week for & & \\  & & & & & & \(6\) months & & \\ \hline \multirow{9}{*}{\
\begin{tabular}{c} [PERSON] et al. \\ (2021) [42] \\ controlled \\ \end{tabular} } & Randomized, & & & & & &
\begin{tabular}{c} 2 \(\,\) probiotic \\ lozenges/day for \\ diabetes \\ old) \\ \end{tabular} & & & & & & & & \\  & & & & & & \\  & & & & & & \\  & & & & & & \\  & & & & & & \\ \hline \hline \end{tabular}
\end{table} 
Table 3: _Cont._JH1005's ability to superinfect the human oral cavity was examined [116]. The results were more than encouraging, as _S. mutans_ levels significantly decreased 7- and 38-fold in the post-treatment period. In contrast, the rest of the subjects' oral ecological flora remained unaffected, thereby satisfying an excellent precondition for a successful replacement therapy that in no way should effector strains unsettle human oral ecological balance to the extent that predisposition to other diseases is possible. The key to achieving a fabricated probiotic combining low acidogenicity and high colonizing capacity was introducing the mutant LDH gene into JH1000 strains [117]. Initially, a natural selection favored the wild-type S.mutans JH1000 occurred by eliminating the mutant gene, suggesting that the LDH gene's mutation was lethal in JH1000 [117, 118]. This problem could be overcome by limiting the glucose supply and by augmenting alcohol dehydrogenase (ADH) activity, which, as found, compensates for LDH deficiency in high sugar concentrations [119]. With the advent of the new millennium, [PERSON] et al. announced the construction of an effector strain, BCS3-L1, thanks to the insertion of the adh B gene of ADH (derived from _Zymomonas mobilis_) to the JH1140 strain (a mutant strain that produces two- to threefold mutacin 1140 than JH1001) [120]. Animal studies highlighted that strain as ideal for replacement therapy inception, as it fulfilled all the prerequisites for an effector strain, which are the significantly reduced pathogenic potential, the selectivity in colonizing the tissues at risk of disease (i.e., the _S.mutans_ niche), genetic stability, superfnecting competency, and prevention of pathogen outgrowth. Targeted mutations were introduced to BCS3-L1 through DNA recombination [50]. These mutations affected the genes dal and come. The dal participates in formation of the bacterial cell wall and the comE gene has a regulatory role in the uptake of exogenous DNA. To date, tests in rats foresee no harmful side effects of A2 JM. Collectively, the A2 JM strain has low acidogenicity, can colonize the oral cavity, produces high levels of MU1140, and is genetically stable. Other strains are also under investigation. These include the LDH-deficient _S. rattus_ JH145, which can displace _S.