Antimicrobial Peptides: Virulence and Resistance Modulation in Gram-Negative Bacteria

Abstract

Growing resistance to antibiotics is one of the biggest threats to human health. One of the possibilities to overcome this resistance is to use and develop alternative molecules such as antimicrobial peptides (AMPs). However, an increasing number of studies have shown that bacterial resistance to AMPs does exist. Since AMPs are immunity molecules, it is important to ensure that their potential therapeutic use is not harmful in the long term. Recently, several studies have focused on the adaptation of Gram-negative bacteria to subinhibitory concentrations of AMPs. Such concentrations are commonly found in vivo and in the environment. It is therefore necessary to understand how bacteria detect and respond to low concentrations of AMPs. This review focuses on recent findings regarding the impact of subinhibitory concentrations of AMPs on the modulation of virulence and resistance in Gram-negative bacteria.

The multifaceted nature of antimicrobial peptides: current synthetic chemistry approaches and future directions

“…187,188 The response of bacterial biofilms to AMPs depends on the concentration, structure, and composition of the AMP. 183 For example, sub-inhibitory concentrations of both polymyxin B and E (colistin) can induce biofilm formation, whereas some cationic AMPs have been reported to prevent biofilm formation or disrupt pre-formed biofilms. [189][190][191]…”

A Synergic Potential of Antimicrobial Peptides against Pseudomonas syringae pv. actinidiae

“…The increase of 3.1 concentration, at non-lethal doses, might, however, interfere with the quorum sensing and/or bacterial virulence involved in inducing an HR in tobacco leaves. As reviewed by Duperthuy [ 86 ], AMPs at sub-inhibitory and sub-lethal concentrations can modulate the virulence in gram-negative bacteria. The AMPs at these concentrations have been reported to downregulate bacterial virulence through sub-cellular interaction [ 87 ], thus deregulating the gene expression involved in virulence and bacteria resistance to environmental stress [ 86 ].…”

“…As reviewed by Duperthuy [ 86 ], AMPs at sub-inhibitory and sub-lethal concentrations can modulate the virulence in gram-negative bacteria. The AMPs at these concentrations have been reported to downregulate bacterial virulence through sub-cellular interaction [ 87 ], thus deregulating the gene expression involved in virulence and bacteria resistance to environmental stress [ 86 ]. These major effects of AMPs’ action at sub-inhibition growth levels have also been hypothesized to be related to quorum sensing, virulence, and biofilm formation.…”

Mammalian Neuropeptides as Modulators of Microbial Infections: Their Dual Role in Defense versus Virulence and Pathogenesis

“…The induction of intrinsic adaptive resistance to AMPs in bacteria is tightly regulated in response to environmental pressure. This response includes: (i) the reduction of bacterial negative cell-surface charge through the incorporation of positively charged molecules into the cell membrane, (ii) efflux pumps to expel AMPs, (iii) proteolytic degradation of AMPs by microbial exotoxins/proteases, (iv) induction of AMP trapping mechanisms [ 134 , 154 ]. When comparing neuropeptides with AMPs in this respect, it should be borne in mind that due to the very low physiological concentration of neuropeptides in mammals, the emergence of selection pressure appears less likely.…”