157
community behaviour in biofilms lead to development of concentration gradient of
substrates leading to localized microenvironments created with biofilm structures.
Although planktonic bacteria have several genes coding for protective stress
responses, they are readily overpowered by a sudden and strong stressful challenge
such as antibiotic exposure. These bacterial populations are killed even before the
response to stress could be triggered (Xu et al. 1998). Whereas in biofilm mode, the
stress response is effectively put into action in certain bacterial cells as a trade-off
to keep the population alive. Matrix of biofilm helps to overcome the environmental
insults such as antibiotics. Although bacteria in planktonic cultures can also counter
balance the antibiotic effects, ability of these single cells in not enough to tolerate
these insults for long, In case of biofilms, the community behaviour gives the advantage of group activity to overcome the effects of antimicrobials by either slow or
blocked penetration of antibiotics (Stewart 2003). Gradients of nutrient and oxygen
created within biofilms assist asynchronous growth of non-dividing populations that
are highly drug tolerant. On one hand phenotypically diverse population of bacteria
within biofilm demonstrates quorum mediated coordination, on other hand these
bacteria reprogramme genes for selective growth of resilient stress enduring cells. A
fraction of cells (≈0.01%) are physiologically different compared to the parent cells
but are genetically similar and are called “persisters”. Although highly drug tolerant, unlike mutant cells persisters are susceptible to minimal inhibitory concentrations of antibiotic under favorable growth conditions (Balaban et al. 2019). These
cells are metabolically inactive with modified toxin antitoxin machinery and are
highly tolerant to high doses of antibiotics. The hipBA toxin antitoxin system was
first demonstrated to have a role in persister formation (Falla and Chopra 1998). A
stringent response alarmone ppGpp, which is present in almost all the bacteria and
plays a critical role in persister cell formation. In addition, SOS activation in bacteria also participate in persistence (Maisonneuve and Gerdes 2014).
7.5 Biofilm Controlling Strategies
Bacteria closely associated with biofilms exhibit enhanced tolerance to antimicrobial agents compared to the free living planktonic bacteria. Thus, physical tolerance
may be re-induced by effective disruption of the bacterial biofilms. To prevent biofilm development cell-cell communication can be an effective target which bacteria
frequently used to reach a threshold concentration. Moreover, extracellular polymeric matrix which stabilizes the biofilms can be targeted which may lead to the
weakening of the biofilm that may eventually lead to disruption. Such altered biofilm architecture may allow effective penetration and drug infiltration to the interior
of the biofilm improving the efficacy of the antibiotics. Likewise, it might cause
enhanced localization of polymorphonuclear leukocytes responsible for phagocytosis mediated removal of pathogenic bacteria. Such weakened biofilm release bacteria, which are more susceptible to antibiotics and immunological response.
7 Control of Bacterial Biofilms for Mitigating Antimicrobial Resistance
community behaviour in biofilms lead to development of concentration gradient of
substrates leading to localized microenvironments created with biofilm structures.
Although planktonic bacteria have several genes coding for protective stress
responses, they are readily overpowered by a sudden and strong stressful challenge
such as antibiotic exposure. These bacterial populations are killed even before the
response to stress could be triggered (Xu et al. 1998). Whereas in biofilm mode, the
stress response is effectively put into action in certain bacterial cells as a trade-off
to keep the population alive. Matrix of biofilm helps to overcome the environmental
insults such as antibiotics. Although bacteria in planktonic cultures can also counter
balance the antibiotic effects, ability of these single cells in not enough to tolerate
these insults for long, In case of biofilms, the community behaviour gives the advantage of group activity to overcome the effects of antimicrobials by either slow or
blocked penetration of antibiotics (Stewart 2003). Gradients of nutrient and oxygen
created within biofilms assist asynchronous growth of non-dividing populations that
are highly drug tolerant. On one hand phenotypically diverse population of bacteria
within biofilm demonstrates quorum mediated coordination, on other hand these
bacteria reprogramme genes for selective growth of resilient stress enduring cells. A
fraction of cells (≈0.01%) are physiologically different compared to the parent cells
but are genetically similar and are called “persisters”. Although highly drug tolerant, unlike mutant cells persisters are susceptible to minimal inhibitory concentrations of antibiotic under favorable growth conditions (Balaban et al. 2019). These
cells are metabolically inactive with modified toxin antitoxin machinery and are
highly tolerant to high doses of antibiotics. The hipBA toxin antitoxin system was
first demonstrated to have a role in persister formation (Falla and Chopra 1998). A
stringent response alarmone ppGpp, which is present in almost all the bacteria and
plays a critical role in persister cell formation. In addition, SOS activation in bacteria also participate in persistence (Maisonneuve and Gerdes 2014).
7.5 Biofilm Controlling Strategies
Bacteria closely associated with biofilms exhibit enhanced tolerance to antimicrobial agents compared to the free living planktonic bacteria. Thus, physical tolerance
may be re-induced by effective disruption of the bacterial biofilms. To prevent biofilm development cell-cell communication can be an effective target which bacteria
frequently used to reach a threshold concentration. Moreover, extracellular polymeric matrix which stabilizes the biofilms can be targeted which may lead to the
weakening of the biofilm that may eventually lead to disruption. Such altered biofilm architecture may allow effective penetration and drug infiltration to the interior
of the biofilm improving the efficacy of the antibiotics. Likewise, it might cause
enhanced localization of polymorphonuclear leukocytes responsible for phagocytosis mediated removal of pathogenic bacteria. Such weakened biofilm release bacteria, which are more susceptible to antibiotics and immunological response.
7 Control of Bacterial Biofilms for Mitigating Antimicrobial Resistance