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Hops are known to have antimicrobial properties against Gram-positive bacteria. This includes bacteria which that can be present in beer both as spoilage organisms and as intentionally added in sour and mixed fermentation beer such as ''[[Lactobacillus]]'' and ''[[Pediococcus]]''. Certain other bacteria found in beer such as ''Acetobacteraciae'' are Gram-negative and are not susceptible to the antimicrobial properties of hops<ref name="Hough_1957">[https://onlinelibrary.wiley.com/doi/pdf/10.1002/j.2050-0416.1957.tb06267.x J. S. Hough, B.Sc, Ph.D., G. A. Howard, M.Sc., Ph.D., and C. A. Slater, Ph.D. 1957.]</ref>. Certain Gram-positive bacteria are known to be more resistant to the antimicrobial effects of hops. Multiple mechanisms have been proposed to explain why hops are antimicrobially active.

One mechanism of the antimicrobial activity of hops is due to the role of alpha acids and similar hop acids (such beta acids and iso-α-acids) as ionophores, or compounds which can transport ions across cell membranes<ref name="Fernandez and Simpson, 1993"> [http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2672.1993.tb02782.x/full Fernandez and Simpson (1993)] </ref> <ref name="Sakamoto and Konings, 2003"> [http://www.sciencedirect.com/science/article/pii/S0168160503001533 Sakamoto and Konings (2003)] </ref>. The protonated iso-α-acid (the form of the acid with an associated H+ ion, an H+ ion is a proton) is the antimicrobially active form. This means that for a beer with a given iso-α-acid concentration, the antimicrobial effects will be stronger at lower pH values because a greater percentage of the acid will be protonated. Protonated iso-α-acids act against bacteria by crossing into the cell and dissociating (releasing H+ ions from the iso-α-acid), therefore disrupting the cellular proton gradient which is necessary for cells to function, before binding an equal charge in metal ions and crossing back out of the cell. Cells with resistance to hop bitter acids are better able to eject disassociated iso-α-acids from the cell and therefore preserve their proton gradients. The mechanism to expel iso-α-acids appears to be specific toward this type of compound rather than by a more general antimicrobial resistance mechanism such as multi-drug resistant bacteria possess<ref name="Sakamoto and Konings, 2003"/>. Hop resistant bacteria cultured in the absence of hop acids can lose their resistance if grown in an environment without antibacterial hop compounds<ref name="Fernandez and Simpson, 1993"/> and some hop resistant microbes need to be acclimated to hop acids by growth in sub-limiting levels of antibacterial acids before they are able to resist higher levels<ref name="Sakamoto and Konings, 2003"/>.

Another antimicrobial mechanism resulting from oxidative stress has been attributed to both iso-α-acids and humulinic acids<ref name="Schurr et al, 2015"> [http://www.sciencedirect.com/science/article/pii/S0740002014002470 Schurr et al., (2015)] </ref>. Humulinic acids are either not bitter tasting or much less bitter than iso-α-acids but are similar in structure to and are formed from the degradation of iso-α-acids as well as during the aging of hops <ref>[https://www.sciencedirect.com/science/article/abs/pii/S0040402001981992 The absolute configuration of the isohumulones and the humulinic acids. D.De Keukeleire, M.Verzele. 1971. https://doi.org/10.1016/S0040-4020(01)98199-2.]</ref>. This oxidative stress-driven antimicrobial activity is due to the potential for oxidation-reduction (redox) reactions within bacterial cells between Mn2+ ions and these specific hop acids. The redox potential is due to different conditions inside (higher pH, higher Mn2+) and outside (lower pH, lower Mn2+) of the bacterial cell<ref name="Behr and Vogel, 2010"> [http://aem.asm.org/content/76/1/142.short Behr and Vogel, (2010)] </ref><ref name="Schurr et al, 2015"/>. Iso-α-acids or humulinic acids passing into the cell, form complexes with Mn2+ and transfer electrons out of the cell<ref name="Behr and Vogel, 2010"/>. By targeted molecular modifications [http://www.sciencedirect.com/science/article/pii/S0740002014002470 Schurr et al. (2015)] determined that the Mn oxidative stress-driven antimicrobial effect of iso-α-acids was more important than the antimicrobial effect of the ionophore proton transfer discussed above in the overall antimicrobial activity of hops. Thus, the antimicrobial effects of humulinic acids have been found to be even stronger than iso-alpha acids, suggesting that aged hops retain at least some antimicrobial properties at least partially from humulinic acids <ref name="Schurr et al, 2015"/>.

The oxidized forms of hop acids have been shown to have a limited inhibitory effect on Gram-positive bacteria. This might explain the anecdotal experiences of some brewers that have tried using aged hops that were high alpha varieties and produced beer that wasn't sour. Stevens et al. (1961) reported that a strain of ''Lactobacillus'' that was cultured from infected beer was inhibited by alpha acids at 40 ppm, beta acids at 10 ppm, iso-alpha acids at 160 ppm, and oxidized beta acids (cohulupone) at 200 ppm. So, while the oxidized beta acids had the least inhibitory power, a high concentration was still inhibitory <ref name="Stevens_1961">[https://onlinelibrary.wiley.com/doi/pdf/10.1002/j.2050-0416.1961.tb01830.x R. Stevens, Ph.D., F.R.I.C., and D. Wright, Ph.D. 1961.]</ref>. Oxidized alpha acids (humulinones) have only been tested for antibacterial properties at a concentration of 50 ppm or less. At 50 ppm, oxidized alpha acids were not able to inhibit two strains of ''Lactobacillus'' that were isolated from infected beer, as reported by Hough et al. (19561957) <ref>[https://onlinelibrary.wiley.com/doiname="Hough_1957" /pdf/10.1002/j.2050-0416.1957.tb06267.x J. S. Hough, B.Sc, Ph.D., G. A. Howard, M.Sc., Ph.D., and C. A. Slater, Ph.D. 1957.]</ref>. See [[Hops#Acids_2|oxidized hop acids]] for more information on oxidized hop acids.