Quorum sensing (QS) in Pseudomonas aeruginosa coordinates the expression of virulence factors, such as exoproteases and siderophores, that are public goods utilized by the whole population of bacteria, regardless of whether they invested or not in their production. These public goods can be used by QS defective mutants for growth, and since these mutants do not contribute to public goods production, they are considered social cheaters. Pyocyanin is a phenazine that is a toxic, QS-controlled metabolite produced by P. aeruginosa. It is a redox-active compound and promotes the generation of reactive oxygen species; it also possesses antibacterial properties and increases fitness in competition with other bacterial species. Since QS-deficient individuals are less able to tolerate oxidative stress, we hypothesized that the pyocyanin produced by the wild-type population could promote selection of functional QS systems in this bacterium. Here, we demonstrate, using competition experiments and mathematical models, that, indeed, pyocyanin increases the fitness of the cooperative QS-proficient individuals and restricts the appearance of social cheaters. In addition, we also show that pyocyanin is able to select QS in other bacteria such as Acinetobacter baumannii.
Aim As options to treat recalcitrant bacterial infections which are increasingly limited due to multidrug‐resistant strains, searching for new, effective antibacterial compounds is necessary. One strategy is to generate treatment alternatives by drug repurposing. Methods and Results In this work, phenotypic microarrays were used for the screening of miscellaneous compounds against the growth and biofilm formation of Acinetobacter baumannii, an important emergent multidrug‐resistant opportunistic pathogen. The results showed that the phenothiazine derivatives, such as promethazine, trifluoperazine, thioridazine, and chlorpromazine, inhibited the growth of antibiotic‐sensitive and multidrug‐resistant strains (showing minimal inhibitory concentrations ranging from 0·05 to 0·6 g l−1 and minimal bactericidal concentrations ranging from 0·1 to 2·5 g l−1). All phenothiazine derivatives were active against biofilm cells (with minimal biofilm eradication concentrations ranging from 0·5 to >3 g l−1). Chlorpromazine promoted reactive oxigen species (ROS) production, and cell membrane and DNA damage. Chlorpromazine showed synergy with antibiotics such as ceftazidime, meropenem, and colistin and was an effective treatment for experimentally infected Galleria mellonella when combined with ceftazidime. Conclusions It was demonstrated that phenothiazine derivatives, especially chlorpromazine, are drugs with attractive antibacterial properties against nosocomial MDR strains of A. baumannii, by generating ROS and cell membrane and DNA damage. Significance and Impact of the Study The present study indicates that repurposing phenothiazine derivatives for treating recalcitrant infections by A. baumannii could be promising.
7 January 2013 in Biological Journal of the Linnean Society
Several arguments have been put forward to explain how sexual selection drives the evolution of sexual trait allometry, especially hyperallometry. The ‘positive allometry theory’ suggests that hyperallometry is a rule in all-secondary sexual traits, whereas the ‘display hypothesis’ suggests that only males in good condition will exhibit hyperallometric sexual display traits. In the present study, we investigated: (1) the condition-dependence nature (by using two diet treatments that varied in the amount of food provided to the larvae) of a sexually selected trait (wing pigmentation; WP) in recently-emerged adults of the American rubyspot damselfly, Hetaerina americana, and (2) the scaling relationship between WP and body size (wing and body length) in the rubyspot damselflies H. americana and Hetaerina vulnerata, according to alternative reproductive tactics (ARTs; territorial and nonterritorial males). First, we found support that indicated that diet positively affected WP length, although there was no significant WP allometric pattern in relation to diet regimes. Second, WP was hyperallometric in both Hetaerina species. WP size was similar between ARTs and, in H. americana (but not H. vulnerata), nonterritorial males showed steeper slopes than territorial males when wing length was used. The results obtained support the notion that sexual traits are hyperallometric, although there is no clear pattern in relation to ARTs.