JAC Advance Access originally published online on June 10, 2008
Journal of Antimicrobial Chemotherapy 2008 62(2):428-429; doi:10.1093/jac/dkn220
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Letters to the Editor |
Concerns of using sialidase fusion protein as an experimental drug to combat seasonal and pandemic influenza—author's response
Z-BioMed Inc., 15725 Crabbs Branch Way, Rockville, MD 20855, USA
* Tel: +1-301-258-8968; Fax: +1-301-260-0622; E-mail: hzhang{at}zbiomed.com
Keywords: neuraminidase , pathogenic factor , S. pneumoniae
In my Leading article, I discussed 12 papers that studied bacterial infection.1 In their commentary on my article, Nicholls et al.2 chose to address only one of them. Studies by several groups using different animal models have demonstrated that influenza virus infection contributes significantly to secondary bacterial pneumonia and that neuraminidase activity in influenza viruses is a predictor of mortality from secondary bacterial pneumonia.3–6 Peltola et al.4 concluded in one of their papers ‘This action of NA also promotes adherence and invasion of Streptococcus pneumoniae, because cleavage of sialic acid from the surface of host cells exposes cryptic receptors for S. pneumoniae. Bacteria that can successfully invade the lower respiratory tract typically express NA for this purpose’.
The fact that influenza A viruses, including recent H3N2 clinical isolates, can infect desialylated cells clearly demonstrates that sialic acid-independent entry can occur,7 but this should not be misconstrued as ‘influenza virus (IFV) receptors may be different from sialic acids (SA)’.
Nicholls et al.2 provided data on sialidase treatment and bacterial adherence to address some of the concerns I raised. However, I have some specific concerns regarding this. Figure 1 in their comment has no quantification and there is a clear increase of DSA and PNA binding after DAS181 treatment. To describe each of these as a ‘modest’ increase is subjective and debatable; indeed, the MALDI-MS data are not quantitative and the relative amounts were not disclosed. The statement by Nicholls et al.2 that DAS181 treatment did not affect S. pneumoniae binding ‘over a broad range of bacterial input’ is inaccurate as their Figure 2 shows that at lower bacterial doses there was an apparent increase (P < 0.05).
I believe that the concerns raised in my original article remain and warrant further consideration and investigation to determine their ramifications.
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H. Z. has shares in Z-BioMed Inc., which is involved in the area of influenza research.
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1 Zhang H. Concerns of using sialidase fusion protein as an experimental drug to combat seasonal and pandemic influenza. J Antimicrob Chemother (2008) 62:219–23.
2
Nicholls JM, Aschenbrenner LM, Paulson JC, et al. Comment on: Concerns of using sialidase fusion protein as an experimental drug to combat seasonal and pandemic influenza. J Antimicrob Chemother (2008) 62:426–8.
3 McCullers JA, Bartmess KC. Role of neuraminidase in lethal synergism between influenza virus and Streptococcus pneumoniae. J Infect Dis (2003) 187:1000–9.[CrossRef][Web of Science][Medline]
4 Peltola VT, Murti KG, McCullers JA. Influenza virus neuraminidase contributes to secondary bacterial pneumonia. J Infect Dis (2005) 192:249–57.[CrossRef][Web of Science][Medline]
5 LeVine AM, Koeningsknecht V, Stark JM. Decreased pulmonary clearance of S. pneumoniae following influenza A infection in mice. J Virol Methods (2001) 94:173–86.[CrossRef][Web of Science][Medline]
6 Braun LE, Sutter DE, Eichelberger MC, et al. Co-infection of the cotton rat (Sigmodon hispidus) with Staphylococcus aureus and influenza A virus results in synergistic disease. Microb Pathog (2007) 43:208–16.[CrossRef][Web of Science][Medline]
7
Stray SJ, Cummings RD, Air GM. Influenza virus infection of desialylated cells. Glycobiology (2000) 10:649–58.
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