Unifying mechanism for bacterial cell signalers (4,5-dihydroxy-2,3-pentanedione, lactones and oligopeptides): electron transfer and reactive oxygen species. Practical medical features

Abstract

Cell signaling has attracted much attention involving higher organisms, and more recently is of considerable interest concerning involvement in the bacterial realm. Many aspects can apply, including quorum sensing. Of the participating molecules, designated autoinducers, 4,5-dihydroxy-2,3-pentanedione (DPD) is one of the most important. It is in equilibrium with a furanone and a furanosyl-borate diester (AI-2). A prior hypothesis for cell signaling in higher organisms invoked a key role for electron transfer (ET) and reactive oxygen species (ROS), as well as conduits, relays and electrical effects. The principal ET functionalities are quinones, metal complexes, ArNO(2), and iminium species. A lesser known type is the alpha-dicarbonyl class. Diacetyl, a member, as well as its imine derivatives, can serve as a model for DPD, since the parent possesses a reduction potential amenable to ET in the biological domain. Hence, it is conceivable that DPD and its imine derivatives may be involved in ET-ROS processes. Presence of hydroxy groups should facilitate ET by DPD vs. diacetyl. Extensive prior literature supports participation of ET functionalities in action of therapeutic drugs, toxins and various illnesses. This biochemical behavior also applies to the alpha-dicarbonyl parent models. A second important bacterial autoinducer is the lactone category. Although ET functionality is lacking, the presence of the 1,3-dicarbonyl structure can provide a site for avid chelation with redox metal, e.g., iron or copper, followed by ET-ROS. Findings with added iron furnish support for the proposal. Oligopeptides comprise the third principal type of bacterial signaling agent. A prior review incorporates these within the theoretical framework based on ET by redox amino acids and redox enzymes. In recent years there has been a rapid increase in resistance to antibiotics by pathogenic bacteria. Infectious diseases are the leading cause of death worldwide and the third leading cause in the US. An alternate approach to antibiotics that are becoming less and less effective is to attenuate bacterial virulence. Bacterial infections appear to be importantly associated with biofilm formation. Since quorum sensors play a crucial role in this connection, they provide attractive targets for much-needed, novel approaches. Two of the main autoinducers investigated are the AHL and AI-2 systems. This review summarizes the literature, mostly recent, on this topic. Leads are provided by higher organisms that appear to have evolved means for disrupting bacterial cell communication and, hence, escape colonization. The main types in this category are the furanones, for which both natural and synthetic types have been investigated with promising results.