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####  INSTITUTE OF AGRICULTURE AND NATURAL RESOURCES

DEPARTMENT OF PLANT PATHOLOGY

October 24, 2007

Docket No. APHIS-2007-0033

Regulatory Analysis and Development

PPD, APHIS, Station3A-03.8

4700 River Road Unit 118

Riverdale, MD 20737-1238

Comments refer to Docket no. APHIS-2007-0033: Proposed Rule

Dear Readers:

First, I commend the agency for open review and revision of the Select
Agent and Toxin List. It appears to be done principally on the basis of
science and potential harm to U.S. agriculture and the economy.

I speak to the PPQ Select Agents and Toxins. I support the removals and
additions, with the possible exception of *Xanthomonas oryzae* pv.
*oryzae*. The case is not well made that the pathovar presents a
critical threat to U.S. rice production, which is a commodity that can
be readily and economically imported from many sources.

Otherwise, I speak specifically in support of *Rathayibacter toxicus*
(syn. *Clavibacter toxicus*). This bacterium causes gumming disease not
only in ryegrass as noted, but other grasses as well, including those
grown in the U.S. In keeping with other listing, it would be helpful to
the reader to indicate that its principal known area of presence is in
Australia, but has also been reported in South Africa. Under natural
conditions, these bacteria require nematodes for transmission,
principally, but not solely Anguina spp.

The toxins produced by the bacterium are apparently under the control of
a bacterial virus, pointing out the hugely complex life cycle of this
bacterium and its glycolipid toxins, given the name corynetoxins.
Strictly speaking, these toxins are not considered neurotoxins, despite
their leading to neurological symptoms of staggering and other loss of
control in sheep and cattle that may graze upon infected plants. There
is more than one toxin produced, hence the reference to corynetoxins,
which inhibit glycoprotein synthase, causing defective formation of
various blood components of the reticulo-endothelial system (see
Cheeke). The toxins are most closely related to tunicamycins, highly
unusual and toxic (to humans) nucleotide antibiotics (see Price and
Tsvetanova).

Thus, the bacterium can colonize and produce toxins in a wide range of
cereals and fodder grasses, including cereal species consumed by humans.
Moreover, since these are heat stable, highly toxic (lethal dose for
sheep is 3-6mg/kg body weight) and bind irreversibly to a transferase
enzyme responsible for n-glycoslyation of proteins, deliberate release
of such toxins could have lasting effects, especially in food products
(see Jago references).

The presence of this bacterium could curtail sheep and cattle production
in some areas. No known resistant varieties are currently available and
disease management, as noted in the Proposed Rule, has been expensive
and difficult. Symptoms in cattle may resemble mad-cow disease and thus
cause panic in the livestock sector. Hay and straw may be contaminated
and then be subject to quarantine or shipment constraints. Thus, the
economic damage may be both direct and indirect.

These articles provide some information on the pathogen as well as
references for the comments made above.

Agarkova, I.V., A.K. Vidaver, E.N. Postnikova, I.T. Riley and N.W.
Schaad. 2006. Genetic characterization and diversity of Rathayibacter
toxicus. Phytopathology 96:1270-1277.

Cheeke, P.R., 1995. Endogenous toxins and mycotoxins in forage grasses
and their effects on livestock.

Jago, M.V. and C.C.J. Colvenor. 1987. Tunicamycinand corynetoxin
poisoning in sheep. Australian Veterinary Journal 65: 232-235.

Jago, M.V., A.L. Payne, H.E. Peterson and T.J. Bagust. 1983. Inhibition
of glycosylation by corynetoxin, the causative agent of annual ryegrass
toxicity: a comparison with tunicamycin. Chemical Biological Interaction
45: 223-234.

Price, N., P.J. and B. Tsvetanova. 2007. Biosynthesis of the
tunicamycins: A review. J. Antibiot. 60: 485-491.

Sincerely,

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Anne Vidaver

Professor