On the antibiotic frontier.

Abstract

In their article “Exploitation of mammalian host cell functions by bacterial pathogens” (2 May, p. 718), B. Brett Finlay and Pascale Cossart state (p. 718), “No new class of antibiotic has been discovered in the past three decades, and derivatives of current antibiotics soon encounter resistance.” During the past 15 years, a group of small cationic antibiotic peptides has been shown to be produced by several animal species, including the cecropins of insects, the magainins of amphibian skin, and the defensins of mammalian neutrophils ([1][1]). The simple chemical structures of many of these antibiotics enabled the use of solid-phase peptide synthesis technology to rapidly create thousands of structural analogs and derivatives, some of which are currently in clinical trails (2). 1. [↵][2]1. R. E. W. Hancock , Lancet 349, 418 (1997). [OpenUrl][3][CrossRef][4][PubMed][5][Web of Science][6] 2. 1. H. G. Bowman 2. et al. , FEBS Lett. 259, 103 (1989). [OpenUrl][7][CrossRef][8][PubMed][9][Web of Science][10] # {#article-title-2} We agree with Wade's statement regarding the antibacterial activity of small cationic peptides and their promise as therapeutic agents. In our article, our statement referred to antibiotics that are currently in clinical use—no new chemical class of antibiotic has been introduced into clinical practice since 1981. At present, only one cationic peptide has passed phase III trials and shows equivalence to a quinolone against a localized infection, although there are several others under consideration. Unfortunately, there are few other new types of antibiotics close to clinical use, although there are many compounds that are under development (1). These include a small number of protein synthesis and cell wall inhibitors. Lipid A inhibitors are in early stages, and other drugs under development are derivatives of existing antibiotics (such as vancomycin). The lack of new types of antibiotics emphasizes the need to understand the mechanisms of bacterial pathogenicity, which can then be applied to developing new therapeutics. 1. R. E. W. Hancock, Clin. Inf. Dis. 24 (suppl. 1), S148 (1997). [1]: #ref-1 [2]: #xref-ref-1-1 View reference 1 in text [3]: {openurl}?query=rft.jtitle%253DLancet%26rft.stitle%253DLancet%26rft.aulast%253DHancock%26rft.auinit1%253DR.%2BE.%26rft.volume%253D349%26rft.issue%253D9049%26rft.spage%253D418%26rft.epage%253D422%26rft.atitle%253DPeptide%2Bantibiotics.%26rft_id%253Dinfo%253Adoi%252F10.1016%252FS0140-6736%252897%252980051-7%26rft_id%253Dinfo%253Apmid%252F9033483%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [4]: /lookup/external-ref?access_num=10.1016/S0140-6736(97)80051-7&link_type=DOI [5]: /lookup/external-ref?access_num=9033483&link_type=MED&atom=%2Fsci%2F277%2F5324%2F297.4.atom [6]: /lookup/external-ref?access_num=A1997WH29600048&link_type=ISI [7]: {openurl}?query=rft.jtitle%253DFEBS%2BLetters%26rft.stitle%253DFEBS%2BLetters%26rft.aulast%253DBoman%26rft.auinit1%253DH.%2BG.%26rft.volume%253D259%26rft.issue%253D1%26rft.spage%253D103%26rft.epage%253D106%26rft.atitle%253DAntibacterial%2Band%2Bantimalarial%2Bproperties%2Bof%2Bpeptides%2Bthat%2Bare%2Bcecropin-melittin%2Bhybrids.%26rft_id%253Dinfo%253Adoi%252F10.1016%252F0014-5793%252889%252981505-4%26rft_id%253Dinfo%253Apmid%252F2689223%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [8]: /lookup/external-ref?access_num=10.1016/0014-5793(89)81505-4&link_type=DOI [9]: /lookup/external-ref?access_num=2689223&link_type=MED&atom=%2Fsci%2F277%2F5324%2F297.4.atom [10]: /lookup/external-ref?access_num=A1989CF90200026&link_type=ISI