title: Bacterial Vaginosis Biofilms: Challenges to Current Therapies and Emerging Solutions.
abstract: Bacterial vaginosis (BV) is the most common genital tract infection in women during their reproductive years and it has been associated with serious health complications, such as preterm delivery and acquisition or transmission of several sexually transmitted agents. BV is characterized by a reduction of beneficial lactobacilli and a significant increase in number of anaerobic bacteria, including Gardnerella vaginalis, Atopobium vaginae, Mobiluncus spp., Bacteroides spp. and Prevotella spp.. Being polymicrobial in nature, BV etiology remains unclear. However, it is certain that BV involves the presence of a thick vaginal multi-species biofilm, where G. vaginalis is the predominant species. Similar to what happens in many other biofilm-related infections, standard antibiotics, like metronidazole, are unable to fully eradicate the vaginal biofilm, which can explain the high recurrence rates of BV. Furthermore, antibiotic therapy can also cause a negative impact on the healthy vaginal microflora. These issues sparked the interest in developing alternative therapeutic strategies. This review provides a quick synopsis of the currently approved and available antibiotics for BV treatment while presenting an overview of novel strategies that are being explored for the treatment of this disorder, with special focus on natural compounds that are able to overcome biofilm-associated antibiotic resistance.
authors.affiliation: Laboratory of Research in Biofilms Rosário Oliveira, Centre of Biological Engineering, University of Minho Braga, Portugal.
authors.forename: Daniela
authors.initials: D
authors.lastname: Machado
authors.affiliation: Laboratory of Research in Biofilms Rosário Oliveira, Centre of Biological Engineering, University of MinhoBraga, Portugal; Instituto de Ciências Biomédicas Abel Salazar, Universidade do PortoPorto, Portugal.
authors.forename: Joana
authors.initials: J
authors.lastname: Castro
authors.affiliation: Health Sciences Research Center, Faculty of Health Sciences, University of Beira InteriorCovilhã, Portugal; Labfit, Health Products Research and Development LdaCovilhã, Portugal.
authors.forename: Ana
authors.initials: A
authors.lastname: Palmeira-de-Oliveira
authors.affiliation: Health Sciences Research Center, Faculty of Health Sciences, University of Beira InteriorCovilhã, Portugal; Child and Woman's Health Department, Centro Hospitalar Cova da BeiraCovilhã, Portugal.
authors.forename: José
authors.initials: J
authors.lastname: Martinez-de-Oliveira
authors.affiliation: Laboratory of Research in Biofilms Rosário Oliveira, Centre of Biological Engineering, University of Minho Braga, Portugal.
authors.forename: Nuno
authors.initials: N
authors.lastname: Cerca
keywords: Gardnerella vaginalis; antibiotics; bacterial vaginosis; biofilms; emerging therapies
references.citation: Epidemiology. 2003 May;14(3):340-8
references.pmid: 12859036
references.citation: Br Med J (Clin Res Ed). 1987 Oct 10;295(6603):886
references.pmid: 3119087
references.citation: Eur J Obstet Gynecol Reprod Biol. 2006 Sep-Oct;128(1-2):40-5
references.pmid: 16460868
references.citation: Obstet Gynecol. 2000 Aug;96(2):256-60
references.pmid: 10908773
references.citation: J Matern Fetal Neonatal Med. 2012 Jul;25(7):1021-4
references.pmid: 21854132
references.citation: J Infect Dis. 2013 May 15;207(10):1491-7
references.pmid: 23431033
references.citation: Lancet. 1991 Feb 2;337(8736):300
references.pmid: 1671134
references.citation: Sex Transm Dis. 2004 Apr;31(4):236-8
references.pmid: 15028938
references.citation: Pathog Dis. 2015 Jul;73(5):null
references.pmid: 25838136
references.citation: Antimicrob Agents Chemother. 1975 May;7(5):672-5
references.pmid: 1096810
references.citation: Infect Immun. 1999 Oct;67(10):5170-5
references.pmid: 10496892
references.citation: Int J Gynaecol Obstet. 2013 Feb;120(2):131-6
references.pmid: 23273888
references.citation: Infect Dis Obstet Gynecol. 2013;2013:909354
references.pmid: 24382940
references.citation: Antimicrob Agents Chemother. 2011 May;55(5):2490-2
references.pmid: 21321147
references.citation: Rev Assoc Med Bras (1992). 2011 Jul-Aug;57(4):415-20
references.pmid: 21876923
references.citation: J Infect Dis. 2006 Jun 1;193(11):1478-86
references.pmid: 16652274
references.citation: Ther Clin Risk Manag. 2009 Jun;5(3):485-9
references.pmid: 19707258
references.citation: J Low Genit Tract Dis. 2015 Apr;19(2):129-34
references.pmid: 24983350
references.citation: Colloids Surf B Biointerfaces. 2011 Aug 1;86(1):58-64
references.pmid: 21497071
references.citation: J Antimicrob Chemother. 2012 Dec;67(12):2870-2
references.pmid: 22855857
references.citation: Sex Transm Dis. 2007 Nov;34(11):864-9
references.pmid: 17621244
references.citation: Antimicrob Agents Chemother. 2014 May;58(5):2747-53
references.pmid: 24566190
references.citation: Int J Gynaecol Obstet. 2005 Mar;88(3):281-5
references.pmid: 15733882
references.citation: J Ethnopharmacol. 2013 Oct 7;149(3):656-67
references.pmid: 23880127
references.citation: J Infect Dis. 2002 May 1;185(9):1307-13
references.pmid: 12001048
references.citation: BMC Infect Dis. 2012 Jun 28;12:148
references.pmid: 22742642
references.citation: Indian J Med Res. 2015 Jun;141(6):799-806
references.pmid: 26205023
references.citation: Am J Obstet Gynecol. 1955 May;69(5):962-76
references.pmid: 14361525
references.citation: J Appl Microbiol. 2008 Apr;104(4):1067-74
references.pmid: 17976171
references.citation: J Obstet Gynaecol Res. 2014 Feb;40(2):583-5
references.pmid: 24118573
references.citation: South Med J. 1999 Mar;92(3):305-7
references.pmid: 10094272
references.citation: Aust Fam Physician. 2009 Jun;38(6):394-7
references.pmid: 19521581
references.citation: Int J Oral Sci. 2011 Apr;3(2):55-65
references.pmid: 21485309
references.citation: Dermatology. 2002;204 Suppl 1:79-85
references.pmid: 12011527
references.citation: Curr Med Chem. 2013;20(23):2914-28
references.pmid: 23651308
references.citation: Am J Obstet Gynecol. 2004 Oct;191(4):1124-9
references.pmid: 15507930
references.citation: Infect Dis Obstet Gynecol. 2012;2012:284762
references.pmid: 23024575
references.citation: J Clin Med Res. 2013 Aug;5(4):309-15
references.pmid: 23864922
references.citation: Arzneimittelforschung. 2010;60(11):675-81
references.pmid: 21175040
references.citation: Iran Red Crescent Med J. 2014 Jul;16(7):e19118
references.pmid: 25237588
references.citation: J Antimicrob Chemother. 2005 Aug;56(2):331-6
references.pmid: 15980094
references.citation: Akush Ginekol (Sofiia). 2013;52(3):19-26
references.pmid: 24283058
references.citation: Annu Rev Med. 2000;51:349-56
references.pmid: 10774469
references.citation: Arzneimittelforschung. 2011;61(4):260-5
references.pmid: 21650086
references.citation: Biomed Res Int. 2015;2015:683640
references.pmid: 26266260
references.citation: J Ethnopharmacol. 2012 Mar 27;140(2):379-83
references.pmid: 22310557
references.citation: J Infect Dis. 2012 Dec 15;206(12):1936-45
references.pmid: 23033146
references.citation: Chin Med J (Engl). 2010 Aug 5;123(15):2051-7
references.pmid: 20819541
references.citation: J Infect Dis. 2014 Aug 15;210(4):593-6
references.pmid: 24596283
references.citation: Arch Gynecol Obstet. 2008 Oct;278(4):341-7
references.pmid: 18236058
references.citation: Arch Gynecol Obstet. 2014 Mar;289(3):479-89
references.pmid: 24170161
references.citation: Obstet Gynecol Int. 2012;2012:147867
references.pmid: 23316237
references.citation: J Appl Microbiol. 2012 Sep;113(3):714-22
references.pmid: 22737982
references.citation: Ann Epidemiol. 2012 Mar;22(3):213-20
references.pmid: 22192490
references.citation: Br Med J. 1960 Sep 24;2(5203):910-1
references.pmid: 14423224
references.citation: Antimicrob Agents Chemother. 2012 Apr;56(4):1756-61
references.pmid: 22252803
references.citation: BMC Microbiol. 2004 Apr 21;4:16
references.pmid: 15102329
references.citation: Minerva Ginecol. 2003 Dec;55(6):483-92
references.pmid: 14676737
references.citation: Anaerobe. 2013 Oct;23:1-4
references.pmid: 23916636
references.citation: Am J Obstet Gynecol. 2003 Jul;189(1):139-47
references.pmid: 12861153
references.citation: Eur J Obstet Gynecol Reprod Biol. 2013 May;168(1):75-9
references.pmid: 23395559
references.citation: BMC Infect Dis. 2015 Jul 03;15:255
references.pmid: 26137971
references.citation: J Infect Dis. 2014 Aug 1;210(3):338-43
references.pmid: 24511102
references.citation: J Infect Dis. 2015 Dec 15;212(12):1856-61
references.pmid: 26080369
references.citation: Colloids Surf B Biointerfaces. 2007 Apr 1;55(2):138-42
references.pmid: 17234391
references.citation: Curr Med Res Opin. 2004 Jun;20(6):849-53
references.pmid: 15200742
references.citation: Anaerobe. 2013 Aug;22:6-13
references.pmid: 23624069
references.citation: Probiotics Antimicrob Proteins. 2015 Jun;7(2):164-71
references.pmid: 25588687
references.citation: Am J Obstet Gynecol. 1981 Sep 15;141(2):145-8
references.pmid: 7282789
references.citation: J Med Life. 2013;6(4):434-6
references.pmid: 24868256
references.citation: Obstet Gynecol. 2005 Nov;106(5 Pt 1):1013-23
references.pmid: 16260520
references.citation: Minerva Ginecol. 2013 Apr;65(2):215-21
references.pmid: 23598785
references.citation: Am J Obstet Gynecol. 2008 Jan;198(1):97.e1-6
references.pmid: 18005928
references.citation: Br J Clin Pharmacol. 2006 Feb;61(2):211-7
references.pmid: 16433875
references.citation: Hum Reprod. 2001 Sep;16(9):1809-13
references.pmid: 11527880
references.citation: Clin Microbiol Infect. 2007 Jul;13(7):657-64
references.pmid: 17633390
references.citation: Br J Vener Dis. 1975 Feb;51(1):51-3
references.pmid: 1092424
references.citation: Am J Obstet Gynecol. 2007 Aug;197(2):170.e1-7
references.pmid: 17689638
references.citation: Probiotics Antimicrob Proteins. 2009 Jan 20;1(1):67-74
references.pmid: 20445810
references.citation: Calif Med. 1969 Jan;110(1):24-7
references.pmid: 5762464
references.citation: Am J Reprod Immunol. 2013 Feb;69(2):150-8
references.pmid: 23167830
references.citation: J Environ Biol. 2014 May;35(3):537-42
references.pmid: 24813010
references.citation: Am J Obstet Gynecol. 2001 Aug;185(2):375-9
references.pmid: 11518895
references.citation: J Clin Gastroenterol. 2014 Nov-Dec;48 Suppl 1:S106-12
references.pmid: 25291116
references.citation: Akush Ginekol (Sofiia). 2008;47(3):7-10
references.pmid: 18756825
references.citation: Arch Gynecol Obstet. 2013 Nov;288(5):1039-44
references.pmid: 23677418
references.citation: Anaerobe. 2005 Jun;11(3):145-53
references.pmid: 16701545
references.citation: ISRN Obstet Gynecol. 2012;2012:183403
references.pmid: 23209922
references.citation: Sex Transm Dis. 2014 May;41(5):290-1
references.pmid: 24722380
references.citation: Gynecol Endocrinol. 2006 Apr;22(4):230-4
references.pmid: 16723311
references.citation: J Appl Microbiol. 2002;93(5):884-93
references.pmid: 12392537
references.citation: Sex Transm Dis. 2009 Nov;36(11):732-4
references.pmid: 19704395
references.citation: Biomed Res Int. 2013;2013:168438
references.pmid: 23984320
references.citation: Am J Obstet Gynecol. 2011 Mar;204(3):211.e1-6
references.pmid: 21167471
references.citation: Infect Dis Obstet Gynecol. 2010;2010:null
references.pmid: 20885970
references.citation: Indian J Pharmacol. 2012 Mar;44(2):243-5
references.pmid: 22529484
references.citation: Arch Gynecol Obstet. 2016 Jan;293(1):101-7
references.pmid: 26142892
references.citation: Mycoses. 2012 May;55(3):199-204
references.pmid: 21793943
references.citation: Antimicrob Agents Chemother. 2010 Feb;54(2):597-601
references.pmid: 20008774
references.citation: Akush Ginekol (Sofiia). 2013;52 Suppl 1:48-53
references.pmid: 24294746
references.citation: Am J Obstet Gynecol. 2014 Nov;211(5):479.e1-479.e13
references.pmid: 24949544
references.citation: J Obstet Gynaecol Res. 2011 Jul;37(7):874-81
references.pmid: 21410839
references.citation: Acta Obstet Gynecol Scand. 2002 Nov;81(11):1006-10
references.pmid: 12421167
references.citation: Arzneimittelforschung. 2002;52(9):706-15
references.pmid: 12404887
references.citation: Lett Appl Microbiol. 2014 Jul;59(1):93-8
references.pmid: 24641524
references.citation: Arch Gynecol Obstet. 2010 Jul;282(1):43-7
references.pmid: 19809829
references.citation: Eur Rev Med Pharmacol Sci. 2003 Sep-Oct;7(5):127-30
references.pmid: 15214587
references.citation: Int J Womens Health. 2011;3:295-305
references.pmid: 21976983
references.citation: Immunology. 2007 May;121(1):140-5
references.pmid: 17250585
references.citation: J Infect Dis. 2010 Dec 15;202(12):1907-15
references.pmid: 21067371
references.citation: Proc Natl Acad Sci U S A. 2011 Mar 15;108 Suppl 1:4680-7
references.pmid: 20534435
references.citation: Braz J Med Biol Res. 2011 Mar;44(3):245-52
references.pmid: 21243318
references.citation: J Nutr. 2007 Mar;137(3 Suppl 2):830S-7S
references.pmid: 17311983
references.citation: J Appl Microbiol. 2015 Sep;119(3):697-710
references.pmid: 26109513
references.citation: Infect Immun. 2006 Aug;74(8):4849-55
references.pmid: 16861673
references.citation: Arch Gynecol Obstet. 2010 Jun;281(6):1065-9
references.pmid: 20012637
references.citation: Infect Dis Obstet Gynecol. 2001;9(1):33-9
references.pmid: 11368257
references.citation: Microb Ecol. 2013 Apr;65(3):773-80
references.pmid: 23250116
references.citation: J Infect Dis. 2015 Jun 15;211(12):1875-82
references.pmid: 25526757
references.citation: Sex Transm Dis. 2015 Jul;42(7):376-81
references.pmid: 26222750
references.citation: Int J Gynaecol Obstet. 2010 Sep;110(3):223-6
references.pmid: 20573348
references.citation: Arch Gynecol Obstet. 2015 Mar;291(3):605-9
references.pmid: 25245669
references.citation: Arzneimittelforschung. 2011;61(2):126-31
references.pmid: 21428248
references.citation: Int J STD AIDS. 2008 Mar;19(3):152-4
references.pmid: 18397551
references.citation: Am J Gastroenterol. 1997 Nov;92(11):2112-3
references.pmid: 9362204
references.citation: Anaerobe. 2015 Dec;36:56-9
references.pmid: 26505928