Pyoverdine is the generic name given to a vast family of fluorescent green-yellowish pigments produced by Pseudomonas species. Pseudomonas aeruginosa is an opportunistic pathogen, particularly infecting humans with compromised natural defenses. These infections result in significantly higher morbidity, longer hospitalization, increased mortality rates and excess health care costs. P. aeruginosa is very difficult to eradicate because of an intrinsic coupled with an adaptive resistance to a wide variety of classical antibiotics. When subjected to iron starvation conditions, Pseudomonas bacteria synthesize pyoverdines, their primary siderophores, to acquire iron from the extracellular medium. These molecules are not only powerful iron(III) scavengers but efficient iron(III) transporters as well. Three distinct structural parts constitute pyoverdines, i.e. (i) the fluorescent chromophore, deriving from a dihydroxyquinoline, attached via its carbonyl group to (ii) a type-specific peptide composed of 6 to 14 amino acids and (iii) a small side chain corresponding to a carboxylic acid derivative. Their chemical structure show three bidentate chelating sites including a catechol and two hydroxamates, leading to an octahedral geometry when complexed to iron(III). While the chromophore group is common to all pyoverdines, their peptide moiety differs among strains and species by the number, length, composition and configuration of amino acids. Following chelation with iron(III), the newly formed pyoverdine-Fe complex is recognized by a specific outer membrane transporter, namely FpvA, and reenters the cell where the iron is released from the pyoverdine into the periplasm for further incorporation into bacterial proteins. The remaining apo-pyoverdine is then recycled and secreted back to the extracellular medium by efflux pumps. Besides, the role of pyoverdines in P. aeruginosa is not only limited to scavenge iron from the bacterial environment. Indeed, these siderophores act as signal molecules for the production of acute virulence factors and are involved in biofilm formation as well. The ongoing expanding pathogenicity of P. aeruginosa has become a major public health problem, and finding alternative strategies to classical antibiotics is urgently needed. Pyoverdines along with the iron pathway recently gained interest among academical researchers as potential new approaches to “fight” the bacteria. This review describes the classification of the nearly 60 pyoverdines identified so far, their structural and chemical properties and their (bio)synthesis. The different mechanisms underlying the steps of a pyoverdine’s life in Pseudomonas are detailed as well: the affinity by which a pyoverdine chelates iron(III), the description of the interactions inducing the siderophore-receptor recognition, the specific transport of the pyoverdine-Fe(III) complex. As pyoverdine production and severe infections are linked, we will also report on situations where pyoverdines are considered as being P. aeruginosa Achilles heel: the propensity of FpvA to transport exo-pyoverdines, organic synthesis of pyoverdines and analogs, grafting of antibiotics on pyoverdines in a Trojan Horse strategy.

The emergence and the dissemination of multidrug-resistant bacteria constitute a major public health issue. Among incriminated Gram-negative bacteria, Pseudomonas aeruginosa has been designated by the WHO as a critical priority threat. During the infection process, this pathogen secretes various virulence factors in order to adhere and colonize host tissues. Furthermore, P. aeruginosa has the capacity to establish biofilms that reinforce its virulence and intrinsic drug resistance. The regulation of biofilm and virulence factor production of this micro-organism is controlled by a specific bacterial communication system named Quorum Sensing (QS). The development of anti-virulence agents targeting QS that could attenuate P. aeruginosa pathogenicity without affecting its growth seems to be a promising new therapeutic strategy. This could prevent the selective pressure put on bacteria by the conventional antibiotics that cause their death and promote resistant strain survival. This review describes the QS-controlled pathogenicity of P. aeruginosa and its different specific QS molecular pathways, as well as the recent advances in the development of innovative QS-quenching anti-virulence agents to fight anti-bioresistance.

More than 40% of the World population is at risk of contracting malaria, which affects primarily poor populations in tropical and subtropical areas. Antimalarial pharmacotherapy has utilised plant-derived products such as quinine and artemisinin as well as their derivatives. However, worldwide use of these antimalarials has caused the spread of resistant parasites, resulting in increased malaria morbidity and mortality. Considering that the literature has demonstrated the antimalarial potential of triterpenes, specially betulinic acid (1) and ursolic acid (2), this study investigated the antimalarial activity against P. falciparum chloroquine-sensitive 3D7 strain of some new derivatives of 1 and 2 with modifications at C-3 and C-28. The antiplasmodial study employed flow cytometry and spectrofluorimetric analyses using YOYO-1, dihydroethidium and Fluo4/AM for staining. Among the six analogues obtained, compounds 1c and 2c showed excellent activity (IC₅₀ = 220 and 175 nM, respectively) while 1a and b demonstrated good activity (IC₅₀ = 4 and 5 μM, respectively). After cytotoxicity evaluation against HEK293T cells, 1a was not toxic, while 1c and 2c showed IC₅₀ of 4 μM and a selectivity index (SI) value of 18 and 23, respectively. Moreover, compound 2c, which presents the best antiplasmodial activity, is involved in the calcium-regulated pathway(s).

Resistance to antimicrobial drugs is currently a serious threat to human health. Consequently, we are facing an urgent need for new antimicrobial drugs acting with original modes of action. The ubiquitous and widely conserved microbial fatty acid biosynthesis pathway, called FAS-II system, represents a potential target to tackle antimicrobial resistance. This pathway has been extensively studied, and eleven proteins have been described. FabI (or InhA, its homologue in mycobacteria) was considered as a prime target by many teams and is currently the only enzyme with commercial inhibitor drugs: triclosan and isoniazid. Furthermore, afabicin and CG400549, two promising compounds which also target FabI, are in clinical assays to treat Staphylococcus aureus. However, most of the other enzymes are still underexploited targets. This review, after presenting the FAS-II system and its enzymes in Escherichia coli, highlights the reported inhibitors of the system. Their biological activities, main interactions formed with their targets and structure–activity relationships are presented as far as possible.

N-methyl-2-pyridone-5-carboxamide (2PY, a major metabolite of nicotinamide, NAM) was recently identified as a uremic toxin. Recent interventional trials using NAM to treat high levels of phosphorus in end-stage renal disease have highlighted new potential uremic toxicities of 2PY. In the context of uremia, the accumulation of 2PY could be harmful—perhaps by inhibiting poly (ADP-ribose) polymerase-1 activity. Here, we review recently published data on 2PY’s metabolism and toxicological profile.