Antibiotic resistance is one of the greatest challenges of the twenty-first century. However, the increasing understanding of bacterial pathogenesis and intercellular communication has revealed many potential strategies to develop novel drugs to treat bacteria-mediated disease. Interference with bacterial virulence and/or cell-to-cell signalling pathways is an especially compelling approach, as it is thought to apply less selective pressure for the development of bacterial resistance than traditional strategies, which are aimed at killing bacteria or preventing their growth. Here, we discuss the mechanisms of bacterial virulence and present promising anti-virulence strategies and compounds for the future treatment of bacterial infections.

/pdf/anti-virulence-strategies-to-combat-bacteria-mediated-1aiyhywclw.pdf

Anti-virulence strategies to combat bacteria-mediated disease

https://zenodo.org/record/1003263/files/Cushnie%20et%20al%20%282011%29%20post-peer%20reviewed%20version.pdf

Recent advances in understanding the antibacterial properties of flavonoids

Hosts and bacteria have coevolved over millions of years, during which pathogenic bacteria have modified their virulence mechanisms to adapt to host defense systems. Although the spread of pathogens has been hindered by the discovery and widespread use of antimicrobial agents, antimicrobial resistance has increased globally. The emergence of resistant bacteria has accelerated in recent years, mainly as a result of increased selective pressure. However, although antimicrobial resistance and bacterial virulence have developed on different timescales, they share some common characteristics. This review considers how bacterial virulence and fitness are affected by antibiotic resistance and also how the relationship between virulence and resistance is affected by different genetic mechanisms (e.g., coselection and compensatory mutations) and by the most prevalent global responses. The interplay between these factors and the associated biological costs depend on four main factors: the bacterial species involved, virulence and resistance mechanisms, the ecological niche, and the host. The development of new strategies involving new antimicrobials or nonantimicrobial compounds and of novel diagnostic methods that focus on high-risk clones and rapid tests to detect virulence markers may help to resolve the increasing problem of the association between virulence and resistance, which is becoming more beneficial for pathogenic bacteria.

Antimicrobial Resistance and Virulence: a Successful or Deleterious Association in the Bacterial World?

Biofilm formation constitutes an alternative lifestyle in which microorganisms adopt a multicellular behavior that facilitates and/or prolongs survival in diverse environmental niches. Biofilms form on biotic and abiotic surfaces both in the environment and in the healthcare setting. In hospital wards, the formation of biofilms on vents and medical equipment enables pathogens to persist as reservoirs that can readily spread to patients. Inside the host, biofilms allow pathogens to subvert innate immune defenses and are thus associated with long-term persistence. Here we provide a general review of the steps leading to biofilm formation on surfaces and within eukaryotic cells, highlighting several medically important pathogens, and discuss recent advances on novel strategies aimed at biofilm prevention and/or dissolution.

/pdf/bacterial-biofilms-development-dispersal-and-therapeutic-28e914uico.pdf

Bacterial Biofilms: Development, Dispersal, and Therapeutic Strategies in the Dawn of the Postantibiotic Era

Bacteria can utilize signal molecules to coordinate their behavior to survive in dynamic multispecies communities. Indole is widespread in the natural environment, as a variety of both Gram-positive and Gram-negative bacteria (to date, 85 species) produce large quantities of indole. Although it has been known for over 100 years that many bacteria produce indole, the real biological roles of this molecule are only now beginning to be unveiled. As an intercellular signal molecule, indole controls diverse aspects of bacterial physiology, such as spore formation, plasmid stability, drug resistance, biofilm formation, and virulence in indole-producing bacteria. In contrast, many non-indole-producing bacteria, plants and animals produce diverse oxygenases which may interfere with indole signaling. It appears indole plays an important role in bacterial physiology, ecological balance, and possibly human health. Here we discuss our current knowledge and perspectives on indole signaling.

Indole as an intercellular signal in microbial communities

The emergence and increasing prevalence of bacterial strains that are resistant to available antibiotics demand the discovery of new therapeutic approaches. Targeting bacterial virulence is an alternative approach to antimicrobial therapy that offers promising opportunities to inhibit pathogenesis and its consequences without placing immediate life-or-death pressure on the target bacterium. Certain virulence factors have been shown to be potential targets for drug design and therapeutic intervention, whereas new insights are crucial for exploiting others. Targeting virulence represents a new paradigm to empower the clinician to prevent and treat infectious diseases.

/pdf/the-biology-and-future-prospects-of-antivirulence-therapies-256kkagw30.pdf

The biology and future prospects of antivirulence therapies

Nature Reviews Microbiology 6, 17–27 (2008), doi: 10.1038/nrmicro1818 In the above article, a mistake was introduced in figure 4. The correct figure is shown below. We wish to apologize to the authors, and to readers, for any confusion caused.

/pdf/erratum-the-biology-and-future-prospects-of-antivirulence-gur02adunh.pdf

Erratum: The biology and future prospects of antivirulence therapies

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The biology and future prospects of antivirulence therapies

Erratum: The biology and future prospects of antivirulence therapies